text:
At The Potted Plant, we take great pride and care in making grave blankets for your loved ones. Each grave blanket is made by hand using only the freshest evergreen boughs of silver fir, noble fir, frasier fir, and western cedar decorated with a mixed green center piece with pine cones and berries. While we feel this is a beautiful blanket in itself, we can customize a blanket for your loved one.
What is a grave blanket?
A grave blanket is a floral display consisting of woven evergreen boughs that covers an entire grave ( or a grave pillow which is placed at the base of the headstone) These displays are popular in northern climates, and they are often placed on graves before the first snow as a symbolic way of keeping deceased loved ones warm. No one truly knows how the tradition started, but the belief is the tradition was brought over from the Scandanvians that settled in the upper midwest.
We have 2 standard sizes available:
2' x 4' (this is the size that is approved for placement at Jefferson Baracks)
3' x 6' This is a full length blanket for a single grave or can be placed at the base of a double headsto
The Potted Plant
1257 St. Peters Cottleville Rd
Cottleville , MO 63376
Phone: 636-447-9000
E-mail: email@example.com
Current Hours:
Mon - Sat 10am - 5pm
Sun 10 am to 4pm


text:
Switch Account
We got our new HD DVR today to replace an HD receiver and older tivo. After getting it to finally activate, I found the DVR full of shows from another user. I cleaned out the shows, the shows set to record, and changed the channel. The unit crashed, bring up the in-home agent. That crashed and I rebooted the unit. For 3+ hours now, we have tried rebooting it, using the pc in-home agent program, and just waiting, but it either gets to the starting up screen and stalls or manages to get a channel for a second before crashing. Any advice? Of course, the tech support is closed now as well. I'm very disappointed in Verizon.
ETA: Plugged the old HD only box in and it works fine, so it has to be the box.
I think you have a bad DVR and should return it. Verizon will hate me for saying this, but if you think about it....it had programs recorded on it...that means that nobody checked it out when it was returned and there is a good chance it was previously returned as a defective unit.
@Hubrisnxs wrote:
for fun, try clearing the hard drive by doing the following.
Most likely it's just flat out a bad stb, and it should be replaced, but in case it's just bad recordings
Access The Diagnostics menu. Press Power (off), Select, Select (from the front panel only).
Complete the following 5 key presses within 5 seconds of each other.
Replay, DVR, DVR, DVR, FiOS TV
Press another button and the LED will display "Clr". Exit the Diagnostics menu and turn on the STB.
Just a note of caution. In the case of this post, this is a good suggestion.
HOWEVER.... If anyone else is reading this post. This is NOT something you want to try in normal troubleshooting. For all intents and purposes this is a complete format of the hard drive on the DVR. This will delete everything on the drive. and I mean everything. It also might necessitate a call to tech support to reactivate the STB. In some cases this reformat sometimes even clears the activation.
So again. In the case of the OP on this thread. Good Idea to try. But for everyone else. Only as a last resort, and then only if you have already tried calling tech support and failed to get results that way.

subset: commoncrawl


text:
Product Description
Our slave pallet is designed to withstand the rigours of day to day life on the ramp.
- 96″ x 125″ (243.8 cm x 317.5 cm), 88″ (223.5 cm) bolt in side guides optional
- 45 -11 gauge x 2.5″ (6.35 cm) diameter galvanized steel rollers mounted on eleven 16″ (40.64 cm) hex shafts
- 4″ (10.16 cm) D section rubber bumpers on both ends
- Tip up type stops, spring loaded to lock in the up position on both ends
- Fork lift tineways located on all four sides
Please contact Aviation Spares & Repairs Limited for more information on the slave pallet. We are here to help with all your GSE requirements.


text:
Listen free for 30 days
Sacrificed: Heart Beyond the Spires
Reunited once more, the crew of Baal's Heart must make the long and treacherous journey south to the towering spires of the Devil's Isles. The path through the mountain range is fraught with peril; mayhem and tragedy plague the pirate ship, but what the men find beyond the spires is the most shocking of all.
In this sequel to the acclaimed Caged, the pirates are dragged into a dangerous new world by Captain Baltsaros's all-consuming obsession. In the midst of terror and chaos, Jon learns that the captain and first mate have been keeping secrets from him. But will the truth tear them apart?
More from the same
What members say
Average customer ratings
5 Stars4
4 Stars0
3 Stars0
2 Stars0
1 Stars0
5 Stars4
4 Stars0
3 Stars0
2 Stars0
1 Stars0
5 Stars4
4 Stars0
3 Stars0
2 Stars0
1 Stars0
Reviews - Please select the tabs below to change the source of reviews.
- jeffrey
- 25-05-17
Pirates are back!!
Any additional comments?
Wow, my favorite pirates are back! Sacrificed: Heart Beyond the Spires by author Bey Deckard is a beautiful tale of love and adventure that takes us through dangerous waters and new lands. To fully appreciate this story readers definitely need to have read, or listened to, Caged: Love and Treachery on the High Seas, the first book in the amazing Baal's Heart series. Narrator Michael Ferraiuolo propels us yet again on this latest fantastic journey with his very impressive and sincere delivery of this historical fiction romance.
Author Bey Deckard has written quite a tale. I can say with much confidence that it is just as good as Caged, and quite possibly my favorite so far in the Baal's Heart series.
The story begins with flashbacks of what's happening now and over the past six weeks since we've last seen Captain Baltsaros and his crew. Baal's Heart is set to sail to the Devil's Isles and the crew quickly obey and gets things ready. Tom and the Captain's relationship is still strained while Tom and Jon seem to grow closer.
The author gives us a world with so many intriguing characters that the audience is privy to all of their thoughts and emotions as the story flows around them.
Each complex and compelling in their own way, Bey has such a way with words that you can't help but be pulled into their world. Told from Jon, Tom and the Captain's points of view the reader/listener gets the thrill of reacting and feeling right along with them.
Captain Baltsaros has a reason for wanting to sail to the Devil's Isles, one that isn't revealed until they are deeply entrenched in a dangerous land. The Captain has many layers and many secrets and in this installment the audience is privy to the feelings and emotions going on in his head. He's frustrated over Tom's numerous refusals, he's jealous of the closeness developing between his first mate and Jon, and he's frightened of his feelings for Jon. He also has to deal with the darkness that lives within him. The author gives us glimpses of these feelings throughout the tale, and with Mr. Ferraiuolo's narration the story simply flows.
I've always been fascinated by Captain Baltsaros and the way the Bey has written him. He's a captivating man with many personalities, some of them good and some of them very questionable. I believe it's a testament to an author's talent when they can create a character and somehow make the reader feel for them even though they may not be such a good person. I must say, readers are in for a real treat when they get to the chapter titled The Menagerie.
Bey Deckard has written some all-time creepy characters that you can't help but be intrigued with and the Emperor in The Menagerie is definitely one of them. This chapter is chilling in the way Captain Baltsaros and the Emperor both talk about human life. This is the darkness that is inside the Captain and he eats it up.
Tom's character has always been special to me. He's brash, sexy and has an air of danger about him. And underneath all of that is a big man who loves fiercely.
In Caged Jon is all timid shyness but in this edition we see another side of him. Being around pirates, and his two lovers, has changed Jon. He's stronger, more confident, and more comfortable in his skin. Although it still bothers him that the crew think of him as a "cabin boy" to both Tom and the Captain, Jon's character grows so much in this story and he really comes into his own.
Right from the start Jon displays a level of dominance over Tom that is all kinds of sexy.
I personally love the progression of Jon's feelings for Tom and Tom's growing feelings for Jon. It's a very sweet romance between these two and Deckard writes such excellent dialogue for his leading men that their interactions are always stimulating…in "every way".
Michael Ferraiuolo's portrayals of Jon and Tom are spot on in my opinion. Bey Deckard pens an erotically charged sex scene with amazing chemistry and Ferraiuolo channels every bit of that energy, becoming each man so expertly. He captures their nuances so perfectly: Making Jon's timid and dominant personalities so delicious - Jon, who can at once be very sweet and in the next breath is tying Tom up and pouring hot wax on his chest; while Tom is stunningly portrayed as playful, confident, rude, and brash.
Between the way Mr. Deckard has written Tom, and Ferraiuolo's narration, I fell in love with Tom all over again.
There is a scene in the story that I had to rewind a time or two. Tom is speaking to Jon and he says, "'You once said you'd kiss me better after a beatin. Can I hold that to ya luv?'" Oh my God! My heart was beating so fast. Good Lord that accent! I absolutely love Tom, and the way the narrator delivers that line had me literally melting!
Mr. Ferraiuolo is perfect for this series and it is attestation of his talent that he can give each character a voice and personality by his narration.
The accents alone fit each man so perfectly, as well as all of the secondary characters; he truly captures the essence of them, making it seem so effortless. From his chilling translation of the Emperor in The Menagerie chapter to the silky smooth and then frighteningly distant voice of the Captain, Ferraiuolo takes Bey's story and makes it come alive!
One of the many things I love about this tale is all of the action, new faces and the inner workings of a ménage. Bey Deckard has written a lush tale of love, sex, and adventure. It's a hard book to put down and I was tempted time and time again to keep listening and forget real life tasks for a while.
It is such an engrossing, heart stopping narrative of epic proportions, with danger around every corner and secrets exposed that cause a devastating fallout.
Jon, Tom and the Captain go through different feelings and emotions during Sacrificed: Heart Beyond the Spires, on their own and in their triad, while dealing with outside forces and many other challenges. Ferraiuolo brings all of them to life in a way that captivates you from beginning to end. Same can be said for Bey Deckard with his talent for giving us another adventurously wild ride into the lives of three beautifully complicated men.
Great writing and great storytelling translates into magic!
1 person found this helpful
- Beach Bum Books
- 01-05-17
Extraordinary performance, compelling story
What made the experience of listening to Sacrificed: Heart Beyond the Spires the most enjoyable?
Michael Ferraiuolo's gift of infusing each character with a unique voice ramped an already compelling tale to another level. This is a strongly character-driven story of betrayal and redemption amidst the backdrop of a mind-bending fantasy landscape that is both familiar and alien.
Who was your favorite character and why?
Jon is still my favorite character: his growth amidst the breaking down of his moral center, tapping into latent sadistic tendencies that strongly conflict with Jon's world view, sets up a powerful Sturm und Drang that drives the plot and provides the glue holding the disparate personalities together.
What about Michael Ferraiuolo's performance did you like?
In a word: incredible. His ability to switch seamlessly between and among all the characters' voices is truly awesome. This is far more than just a "reading"... it is performance art.
Was there a moment in the book that particularly moved you?
When Jon is finally confronted with the ultimate moral choice toward the end of the book, his reality fractures and releases the man he will become. All truly excellent books have that one defining moment: for me, it was that scene with Jon.
Any additional comments?
If you love alternate universe, historical fantasy tales of adventure that are character-driven, intensely sensual and morally conflicted, then the Baal's Heart series is just what you are looking for.
1 person found this helpful


text:
About All-Temp Mechanical Inc
- Family owned and operated.
- Serving customers throughout the Greenville area.
- Founded in 1991.
- Built and impressive list of valuable, loyal customers.
- The Rohrman family values honesty and integrity and has built their company on these principals.
Why Choose All-Temp Mechanical Inc?
- Locally Owned & Operated
- Written Estimates
- High Quality Work


text:
The WSDOT headquarters hydraulics section provides technical support, training and policy in the fields of hydraulics, fish passage, hydrology and stormwater to ensure our roadways provide a safe, effective and efficient movement of people and goods while maintaining the natural movement and treatment of water throughout our watersheds and water bodies.
In addition, the headquarter hydraulics section coordinates and provides technical guidance and policy for research in the fields of hydraulics, fish passage, hydrology and stormwater. Find for more information (pdf 123 kb) about the Hydraulics Section roles and responsibilities in supporting statewide project delivery.
Resource and guidance materials
Precipitation Information
Approved Drawings


text:
My price includes postage and packing within the UK, items usually being despatched within 48 hours of receipt of funds. I am happy to send items abroad but buyers from overseas should contact me for shipping costs and make an additional payment. Buyers are liable for import taxes in their own country where appropriate.
Remember - on most pages you can click pictures to see more photos!
These are photos of the actual model available. Remember that these toys are around 50 years old! All models advertised are original, not restored or repainted unless I have stated otherwise.
These cars are wonderfully photogenic, apart from brown marks on the chrome that some develop! You'll find them in three colours: metallic blue, pale blue and this gold colour.
A popular model with the wonderful trans-o-lite lights front and back, these are still quite reasonably priced.
This is a late edition, with the smart cast wheels and these are particularly clean too. This is in good condition with no scratches and a good tow hook. Good suspension, wheels, screens and tyres.
A nice box, complete but chewed in one place, is included. [Sold]
Pale blue
245-1 | 245-2 | 245-5 |
245-3 | 245-4 | 245-6 | 245-11
Metallic blue
245-7 | 245-8
245-9 green-blue, cast wheels
245-10 | 245-12 metallic blue cast wheels
Gift Set 31 with Dolphin Boat


text:
UCI Track Cycling Workshop is going to be held in the morning of the 23rd March 2011 in Apeldoorn, Netherlands.
This Workshop is organized to follow up matters that were discussed on the Track Cycling Workshop held during the 2009 UCI Track Cycling World Championships in Pruszkow, Poland, as well as discussing new topics imposed by the evolution of Track Cycling.
In order to enable again a fruitful workshop, it has been decided to maintain the restriction of delegates per continent as 4 for Europe, 3 for Asia, 3 for Americas, 2 for Oceania and 1 for Africa.
All NF are required to submit to ACC the identity of their delegates no later than by 11th March 2011. Therefore, should you be interested to attend this workshop, please contact with ACC on the information of the delegate by indicating the first and last names of the delegates together with their role in Track Cycling and the country they represent.


text:
The play started with the 25 hour play-writing competition at the 2013 Toronto Fringe Festival. It was meant to be something I tried for fun, a neat writing challenge, then somehow I won. And they did a public reading directed by a real director with a real cast.
That was such a fun experience, I learned so much working with these people, and everyone involved with the Fringe Festival was incredible, but then what do I do next?
Well I wrote it in 24 hours, it had a pretty good start and was pretty funny but it needed work… months and months of work.
But I did it! And by did it I mean I'll probably do some more rewrites.
We got a crew together. We held auditions. We cast it. We had a read through.
We started rehearsals.
We've even had a photo shoot.
There is still a lot of work left ahead of us but it's coming together so well.


text:
TYM Overdriverer Pedal - NEW!
By Tym Guitars
Sorry, this product is sold out!
Killer new pedal from Tym Guitars in Brisbane. The Overdriverer is based on Tym's ODP666 with a couple of small mods to make it more variable for more options. This is a classic simple LM741 op amp driven circuit with two silicon diodes for clear, crisp clipping. It's one of the great seventies overdrive designs with lots of volume and gain on tap or can be used as a preamp with the gain down and the volume up.
This new series are all hand assembled in Brisbane using the same quality PCB's and components as Tym's current line. They all use powder-coated Hammond style enclosures without printed aluminium faceplates.
Tym's pedal designs are inspired by the classic old units but with modern components and appointments with true bypass, LED's and "Boss" compatible 9 volt adapters. Interesting to note, none of Tym's pedals use batteries.


text:
On Saturday, the Swedish Academy honored the 2016 Nobel Peace Prize winners in a ceremony held in Stockholm. The awards winner for literature, Bob Dylan, was not in attendance due to scheduling conflicts. Patti Smith, who appeared in place of the legendary songwriter, was accompanied by the Philharmonic performing a sparse, sensitive version of Dylan's "A Hard Rain's A-Gonna Fall." During the performance, Smith repeated a line and asked to start the section over again. "I apologize, I'm so nervous!" she admitted. The orchestra obliged and the audience responded with applause.
Patti Smith accepts Bob Dylan's Nobel Peace Prize, performs "A Hard Rain's A-Gonna Fall"
December 12, 2016


text:
Importance of Custom Database Services
Most products are usually generic and while this is great it may not always fit to the needs of your organization. Having customized databases is beneficial for your organization for a variety of reasons and it is something that you should consider for your organization. Some of the benefits of having customized databases are briefly highlighted below.
It is important that data is managed well since it is the lifeblood of any business and ensures that businesses grow and continue to stay innovative. When you are able to customize your data, you are able to organize and report it in a way that you are able to understand it. With the help of filtering interfaces, dashboards, tables as well as reports you are able to know if there are any changes in data even as your team updates the databases.
When you have a customized database, you are able to execute ideas faster and this helps to give you competitive advantage. It is easy to execute ideas fast when you have a customized database and this will ensure that you stay ahead of the curve and that you do not miss business opportunities that if not effected will eventually cripple your business. Once you execute ideas expeditiously, you are able to continue being relevant in the market and this can also help you stand out from your competition.
When you choose to customize your database, you are able to stay at the forefront of technology and this is important and crucial for your business. You are able to carry out projects without the need of specialists when you stay updated with current technology trends. By doing this you end up spending way less than what you would have otherwise spent and this becomes cost effective compared to if you did not have customized databases.
With a customized database, it is easy to get round the clock customer support to ensure that your databases are running smoothly. If you have international clients, it becomes easy to ensure that you are able to serve them well when you have such support. should your databases require attention, you are able to get the assistance you need when you have reliable support.
Since you will be in a position to scale up your business due to the flexibility customized databases have, it becomes cost effective for you. Depending on the resources needed, it becomes easy to scale up or down since you do not have to worry about paying per user. With such arrangements, they can become cost effective for you in the long end and this can be cost effective for your business in the long end.
Why People Think Businesses Are A Good Idea
The Beginners Guide To Resources (What You Need To Know To Get Started)


text:
Simpson Auto Racing Helmets
By Winding Road Staff
Whether you are road racing, doing a track day, running autocross or participating in High Performance Driver Education, you need a helmet. But it can be confusing when it comes to actually buying one. There are a lot of choices and sometimes the differences aren't obvious.
To give you some help, we recently reviewed 45 helmets from Bell, Simpson, Black Armor, Arai and Stilo. We found when testing factors like features, style, weight, fit and price that there were models that stood out. We've picked 10 helmets that cover a range of prices and are the ones we would start with when shopping. You may find that a given helmet doesn't have ideal fit or is missing a feature that is critical for you, but at least you have a way to narrow down you selection process.
As a refresher in factors you need to consider when buying a helmet, you may want to read our Helmet Buyers Guide:
All the helmets below are HANS compatible and Snell SA 2010 rated.
And now, ladies and gentlemen, our helmet picks for the 2015 season:
About 3.7 lb.The Bell Sport is a very nice, classically-styled helmet that really sets the bar for helmets above this price point. Unlike some other inexpensive helmets, this Bell shape is reasonably comfortable for many users. Bell also offers the Sport in a Sport EV model (same price) with an even larger eyeport (many people new to racing find that helmets feel somewhat confining and the larger eyeport helps relieve that feeling – especially if you wear glasses). The Sport is also available in a variety of paint colors and patterns. See all Bell helmets.
About 3.6 lb.Helmet fit is about the most important thing, especially if you race where it is hot or you are in the car for long periods (e.g. ChumpCar). The Bell Sport series is well shaped for more rounded head shapes, but if your head shape is more oval, you may prefer the Simpson Voyager. It has Simpson's largest eyeport, which we've found many new drivers prefer (and is also helpful if you wear glasses). If the Voyager is too narrow and the Bell Sport too wide, you may want to try the Simpson Bandit (0). See all Simpson helmets.
About 3.5 lb.As an update of the 1970's Bell Star, which was a safety breakthrough, we originally chose the Star Classic for Vintage racers looking for something that offered full modern specification but that fit with the vibe of their cars. After trying it, we can also imagine drivers of modern cars just liking the clean look or enjoying the fit (several of our testers thought it was very comfortable). See all Bell helmets.
About 3.4 lb.Warning! Don't try an Arai helmet unless you can live with the price point. Several of our testers found the Arai shape and padding more comfortable than any other and couldn't go back to their previous helmets. You mileage may vary, of course, but consider yourself warned. The GP5W gets you that Arai fit along with a large eyeport. See all Arai helmets.
About 3.3 lb.The Stilo ST4W offers the widest range of optional features in this price range or even higher prices (except for other Stilos). The ST4W can be configured with a built-in radio connector and mic (usable with ear buds or with built in headphones), a hydration port and top air (side air is also possible but then you can't have both comms and hydration). There is an optional eject bladder for safety workers to use to remove the helmet. And Stilo offers a range of full and half visors, plus a peak visor. The ST4W is designed for closed cockpit cars and has a medium eyeport. The related ST4F is for open cars and has a narrow eyeport. See all Stilo helmets.
99If you want a carbon helmet, the Bell RS7, while a bit more expensive than some, fits the most people among "entry level" helmets, in our experience. Carbon is somewhat harder to shape for ideal fit and the complexities of that shaping drive the price up it seems. See all Bell helmets.
About 3.2 lb.The GP6 PED features the famous Arai fit (which is based on ergonomic shape plus softer padding) along with the same shape as their Formula 1 helmets. The GP6 PED includes an optional aero kit for use in open cockpit cars and offers a full range of visor choices and ventilation options. The GP6 PED has a narrow eyeport. See all Arai helmets.
$1855The ST4W Carbon offers everything we love about the ST4W composite: optional comms port/mic, hydration port, forced air, and high comfort. Plus the snazzy Stilo design looks especially cool in exposed carbon weave. The Carbon model shaves a few ounces, which drivers of high-power cars or enduro racers will appreciate. See all Stilo helmets.
About 3 lb.If you love the Arai fit, can live without the optional Stilo features, and want the lightest, strongest helmet possible, then the GP6 RC is for you. Used in F1, the GP6 RC also features a special carbon weave that flexes rather than shatters on impact for great safety. Comes with an aero kit for open cockpit cars. FIA 8860 approved. See all Arai helmets.
About 2.8 lb.If you want it all, this is probably the helmet to have. The feature list is impressive: Communications standard, with headphones optional; Optional hydration port; Optional forced air; Optional eject bladder; FIA 8860 rated and yet the lightest helmet we tested; Comfortable for many users; Wide array of visors and peaks; Wide eyeport.; Aerodynamics kit included. See all Stilo helmets.
Noteworthy Specialty HelmetsRally helmets must meet some special requirements. First you need a helmet set up for communications because electronic driver to co-driver communication is absolutely essential in competition. Second, you want an open-face helmet in case the electronic system breaks down mid-stage (this can be handy for transits, too). Trust us, in a rally car you pretty much can't shout your way past a closed-face helmet. We like this Black Armor Rally Carbon helmet because it meets these requirements, looks slick, and is about half the cost of competing designs. See all Black Armor helmets.In some series, your crew members must wear helmets. The problem with standard helmets is that visibility isn't very good for crew people who do work in tight quarters. Coupled with goggles and a balaclava, this Simpson helmet is specifically designed to solve that problem. It is cost-effective, too. Check your sanctioning body rules to confirm legality in your series. See all Simpson helmets.


text:
The stage is set for the 2017/18 Algerian Cup final as JS Kabylie take on USM Bel Abbes at the Stade du 5 Juillet on Tuesday the 1st of May, with kick-off at 4pm.
JS Kabylie have won the DZ Cup five times, whereas USM Bel Abbes have won it just once. The one time they won it was actually against JS Kabylie, in the 1991 final. Essaid Belkalem will captain the Amazigh outfit in what will be a sold out national stadium.
Both sides currently sit in mid-table in the Algerian league, and both look to be safe from relegation after a rocky season domestically. The winner of the Cup will win a place in the CAF Confederation Cup next year, which is the African version of the Europa League.
USMBA have won every Cup final they have been in, whilst JSK have been in ten finals and lost five of them. As ever, the Algerian army will play an exhibition match on the morning of the game.
JS Kabylie knocked out MC Alger on penalties to reach the final, whereas USM Bel Abbes defeated fifth division CR Zaouia with a late 94th winner. You can follow the game live on our Twitter page; @DZFootball_en.


text:
- IOF International
- IOF Websites
- IOF Microsites
- Member Societies
- Sign In
- Sign Up
- Members Area
You are hereHome - Data & Publications - Progress in Osteoporosis -
Overview, Vol 11, Issue 2
By Ego Seeman Thu, 03/08/2012 - 12:25
Epidemiology – oops, looking in the wrong place
The meeting of minds of the WHO committee many moons ago to establish a definition of osteoporosis as a T-score of <-2.5 SD gave voice to the silent epidemic of bone fragility which predisposes to fractures. That was a good thing but it is not without its limitations. One of the most important problems is the idea that fractures occur mainly in persons with osteoporosis. Over 50% of fractures in the community arise among persons without osteoporosis. Screening programs using a threshold of -2.5 SD will reassure and discharge these individuals. This is the screening paradox, described many years ago by Geoffrey Rose, whose books and papers on the topic are essential reading. Measurement of bone density is not sensitive; nor is it specific, many people with "osteoporosis" do not fracture and do not necessarily have fragile bones.
This point is reinforced by Oyen et al who reported that 40% of 263 women with distal radial fractures did not have osteoporosis. Osteoporos Int 2010;21:1247-55 Oyen et al also reported that of 218 men and 1576 women with distal radial fractures, T-scores <-2.0 and <-2.5 SD at femoral neck was found in 37.7% and 19.6% of men and 51.1% and 31.2% of women, respectively. The risk of hip fracture was for patients with T-score <-2.0 SD were 11.6% and 14.5% and for T-score <-2.5 SD 16.3% and 18.2%, respectively. Osteoporos Int 2010;21:1257-67
The point is made again in a study Pulkkinen et al who reported that in postmenopausal females with cervical (n=39) or trochanteric (n=18) hip fracture and 40 age-matched controls, a BMD T-score of -2.5 discriminated trochanteric fractures from controls (p<0.001); here 17 of 18 occurred in individuals with T-score ≤-2.5. However, only 20 cervical fractures (51.3%) occurred in individuals with BMD in osteoporotic range. Within the nonosteoporotic cervical fracture patients (N=19) and nonosteoporotic controls (N=35), 83.3% were classified correctly based on a model including NSA and FNC, area under the receiver operating characteristics curve being 0.85 for the model, while it was only 0.56 for BMD alone. Osteoporos Int 2010;21:1269-76
Morbidity, mortality and cost – note the nonvertebral fracture burden
There is a perception that vertebral fractures are the flagship of osteoporosis and bone fragility. This is not the case, 80% of all fractures in the community are nonvertebral and these fractures are costly, and more so as a group than hip fractures. Pike et al studied patients with a nonvertebral fracture (NVF). Although hip fractures had highest excess costs, nonvertebral, nonhip fracture patients made up a larger proportion of the sample and were more costly than controls. Comorbidity rates and resource use were higher among NVF patients during second year following an NVF compared with controls. Mean direct excess costs for NVF patients fell from $5267 in the first year to $2072 in the second year after a fracture. Patients with fractures of the pelvis, hip, and femur had the highest excess costs in the second year ($5121, $3930, and $3828, respectively). Osteoporos Int 2011;22:47-56
Song et al studied patients with incident fracture and >12-month pre-period and follow-up period from the incident fracture. Nationally projected annual cost of second fracture was $834 million for patients with commercial insurance and $1.13 billion for Medicare patients. For privately insured patients with hip, vertebral, or NHNV fracture, the 1-year second fracture rate was 8.0%, 5.1%, and 4.0%, and 1-year incremental costs were $47,351, $43,238, and $23,852, respectively; for Medicare patients, the corresponding rates and costs were 8.8%, 9.2%, and 8.2%, and $18,645, $19,702, and $19,697. Bone 2011;48:828-36
Huntjens et al report of 1921 consecutive patients 50+ years having a NVF, nearly one in five patients sustained a subsequent NVF and one in three died within 5 years after an initial NVF. One third of subsequent NVFs and mortality occurred within one year. The risk for a subsequent NVF was 17.6% and was related to age (HR per decade, 1.44). The risk for mortality was 32.3% and was related to age (HR per decade, 2.59), male sex (HR, 1.74), fracture at baseline (HR, 5.56) and subsequent fracture (HR, 1.65). The highest risks were found within the first year (NVFs, 6.4%; mortality, 12.2%) and were related to age and baseline fracture location for mortality. Osteoporos Int 2010;21:2075-82
Heterogeneity in morphology in patients with fractures
The prevailing view is that the large number of persons with BMD in the osteopenia range reflects the fact that they come from the larger pool of individuals in the bell of the bell shaped distribution, rather than from the smaller tail of the distribution. The question is whether these patients have structural abnormalities responsible for bone fragility. Some evidence is available that indeed, these patients have fragile bones but this is not detected by the bone densitometer. These patients have reduced trabecular BV/TV, reduced trabecular number and connectedness. They also have higher intracortical porosity (Seeman, unpublished data).
Persons with fractures are not all the same, the pathogenesis of bone loss and bone fragility differs markedly between individuals with "one or more minimal trauma fractures". Until the structural basis is defined we will be left with the poor sensitivity and specificity of bone densitometry which fails to identify over 50% of all fractures in the community.
An example of this heterogeneity is reported by Parfitt et al, who studied the behaviour of the cellular activity upon the endocortical and trabecular envelopes that determines bone structure in three dimensional space and so its strength. The investigators reported that a combination of defective osteoblast recruitment and premature osteoblast apoptosis account for differing deficits in bone surfaces, the reductions in mean wall thickness and bone formation rate on the cancellous surface, and osteocyte deficiency in cancellous bone. Patients with vertebral fractures had reduced surface extent of osteoblasts, markedly on the cancellous surface, where 75% of the deficit was in intermediate (type III) cells, suggesting earlier transition to type IV (flat) cells and about 25% of the deficit was in cuboidal (type II) osteoblasts, suggesting impaired recruitment. On the endocortical and intracortical surfaces, the deficit was exclusively in type III cells. Mean bone formation rate was reduced by about 18% on the cancellous surface but not on the other two components of the internal surface and was due to a reduction in wall thickness. Bone formation rate was skewed left in the fracture patients. Osteoclast surface was lower on each subdivision. The data emphasise the histologic heterogeneity of postmenopausal osteoporosis. J Bone Miner Res 2011;26:475-85
The purpose of bone remodelling is to remove old or damaged bone. However, what precisely is 'damage'; a crack, dead osteocytes, highly crosslinked bone, abnormalities in mineral content? If damage differs in nature, are the signals to repair it also different? Herman et al reported that fatigue microdamage occurs as either linear microcracks or diffuse sublamellar damage. Activation of resorption correlated to the number of linear microcracks, no activation of resorption occurred in response to diffuse microdamage and there was no change in osteocyte viability in response to diffuse microdamage. Bone 2010;47:766-72
Is cortical but not trabecular bone estrogen sensitive?
Some studies suggest that there is also heterogeneity on bone tissue regarding the response to estrogen and estrogen deficiency. The basis of this notion is that there appears to be little cortical bone loss before menopause; while trabecular bone loss appears to be independent of menopause, decreasing linearly with age and without an apparent acceleration at the time of menopause, at least in cross-sectional studies.
Syed et al studied ovariectomized, or ovariectomized and estrogen-replaced female C57/BL6 mice at 6 months of age. Compared with young mice, aged/sham-operated mice had a 42% reduction in spine BV/TV. Maintaining constant estrogen levels over life in ovariectomized/estrogen-treated mice did not prevent age-related trabecular bone loss. By contrast, lifelong estrogen in ovariectomized mice prevented the age-related reduction in tibial cortical vBMD and thickness. Moreover, as compared with cells from young mice, hematopoietic lineage negative cells from aged/sham-operated mice expressed higher mRNA for osteoblast differentiation and proliferation marker genes. J Bone Miner Res 2010;25:2438-46
Bone is not the centre of the universe
Gerard Karsenty has shifted the position of bone from the centre of the universe to its perhaps rightful position as one of the satellites rotating around the real centre of the universe, energy metabolism. In one of several studies confirming his ideas, Kanazawa et al reported that serum osteocalcin was negatively associated with fasting plasma glucose, HbA(1c), %trunk fat, and homeostasis model assessment (HOMA) for insulin resistance, and positively with HOMA for β-cell function in 101 postmenopausal women and 152 men with type 2 diabetes. In addition, positive association of serum osteocalcin with serum adiponectin was found in postmenopausal women. In the OGTT examinations, subjects were divided into tertiles by their serum osteocalcin levels. Postmenopausal women in the lowest tertile showed hyperglycemia and hyperinsulinemia compared to those in the highest tertile after oral glucose loading. Men in the lowest tertile also exhibited hyperinsulinemia, while hyperglycemia was not found. Serum osteocalcin is positively associated with insulin sensitivity and secretion in Japanese patients with type 2 diabetes. Bone 2011;48:720-5
Schulte et al presented fascinating use of noninvasive direct techniques to derive dynamic bone morphometry. Dynamic measures of bone formation correlated with MAR (R=0.68) and MS (R=0.78). After 4 weeks of loading, newly extracted trabecular BFR and MS were higher in the loading compared to the control group, ES was decreased. This indicates that modelling induced by mechanical loading takes place primarily by increased area, not width of formation packets. Bone 2011;48:433-42
Isaksson et al investigated the humeri from female New Zealand white rabbits of varying age. In mid-diaphyseal cortical bone samples the elastic stiffness increased with age, from 11 days to 6 months, based on the reduced modulus from the indentation probing, the storage modulus from the semidynamic test, and the first elastic parameter from the creep test. These elastic parameters correlated (R=0.88-0.94, p<0.01). Viscoelastic parameters, the phase-shift and time creep constant, decreased with age. For the viscous properties determined by the creep and the semidynamic testing correlated (R=0.90, p<0.01), however, no correlation was found between the phase-shift and the creep time constant. The elastic modulus of bone tissue increased by approximately 60%, whereas the viscoelastic parameters decreased by 10% to 25% during the first 6 months of the rabbit's life. Bone 2010;47:1030-8
Serum sclerostin
Modder et al reported that estrogen (E) treatment of postmenopausal women (n=17) for 4 weeks led to a 27% decrease in serum sclerostin. Similarly, in 59 elderly men, E, not testosterone (T), prevented increases in sclerostin following induction of sex steroid deficiency. In both sexes, changes in sclerostin correlated with changes in resorption, not formation, markers (r=0.62, p<0.001, and r=0.33, p=0.009, for correlations with changes in serum C-terminal telopeptide of type I collagen in the women and men, respectively). Sclerostin levels are reduced by E not T. Changes in sclerostin production may contribute to effects of E on bone resorption. J Bone Miner Res 2011;26:27-34
Macdonald et al reported that in 442 women and 202 men aged 20-99 years, total bone area, which was 33% larger in young men, changed similarly with age in women and men at the DT but increased 17% more in men than in women at the DR. Trabecular number and Tb.Th were higher in young men than in young women at both sites, and with the exception of Tb.Th at the DR, which declined more with age in men (-16%) than in women (-2%, p<0.01), the age-related decline in these outcomes was similar in women and in men. In the cortex, porosity (Ct.Po) was 31% to 44% lower in young women than in young men but increased 92% to 176% more with age in women than in men. The DR cortex carried 14% more load in young women than in young men, and the percentage of load carried by the DR cortex did not change with age in women but declined by 17% in men. FEA-estimated bone strength was 34% to 47% greater in young men, but the predicted change with age was similar by sex. In contrast, the load-to-strength ratio increased 27% more in women than in men with age. J Bone Miner Res 2011;26:50-62
Glucocorticoid-induced autophagy in osteocytes
Xia et al reported that glucocorticoid (GC) induced autophagy preserves osteocyte viability. GC resulted in an increase in autophagy markers and the accumulation of autophagosome vacuoles in vitro and in vivo promoted the onset of the osteocyte autophagy, as determined by expression of autophagy markers in an animal model of GC-induced osteoporosis. An autophagy inhibitor reversed the protective effects of GCs. In contrast, TNFα induced apoptosis but not autophagy. J Bone Miner Res 2010;25:2479-88
Drug therapy - is one plus one more than two or less than two?
Prior or concurrent use of remodelling suppressants may blunt the rise in remodelling markers and BMD produced by PTH1-34. The reasons for this are not understood. The anabolic effects of PTH1-34 are both modelling and remodelling based, but 70% of the effect is reported to be remodelling based and this might explain why there is blunting. When suppression of remodelling occurs with a bisphosphonate, the remodelling based component of the anabolic effect may be lost.
Not all pieces of the puzzle fit. Cosman et al reported the opposite. PTH 1-34 plus zoledronic acid initially produced a greater increase in BMD than PTH1-34. The observations raise many questions. One explanation of may be that the modelling based anabolic effect will occur and produce a net greater benefit than either agent alone. This doesn't quite fit either. If correct, why isn't the same observed with alendronate which should also allow the modelling dependent anabolic effect to proceed? One explanation to reconcile the differing observations is that zoledronic acid is a more potent remodelling suppressant than alendronate – initially. When first administered, the greater remodelling suppression allows porosity produced by remodelling at the time of treatment to go to completion with appearance of fewer new remodelling sites with zoledronic acid than with alendronate. Under these circumstances the rise in BMD may be greater with zoledronic acid plus PTH1-34 than PTH alone because the filling phase occurs without appearance of new remodelling sites. Alendronate suppresses remodelling less than zoledronic acid so porosity decreases less because any decrease in porosity produced by allowing filling of sites excavated at the time of treatment is now offset by more new pores as alendronate suppresses remodelling by only 50%. What is needed to sort this out is a study randomizing patients to alendronate plus PTH vs. zoledronic plus PTH, with a PTH alone arm and measurements of bone microarchitecture and tissue density to examine the effects of remodelling on any continued remodelling despite treatment on both porosity and tissue mineralization density. Densitometry is not going to help here. J Bone Miner Res 2011;26:503-11
The real question this study raises is why do these studies at all. The justification for studies comparing the BMD response of single vs. combined therapy is that if a greater BMD change is observed with one regimen over another, this will mean that the fracture risk reduction is greater. There is no evidence for this. A change in BMD provides little, if any, insight into the effects of combined therapy on the material composition and structure of bone over single therapy. Nor does it provide insight regarding potentially superior antifracture efficacy over single therapy.
Suppression or blunting of response to teriparatide (TPTD) is not always seen. Stepan et al reported the response to TPTD was not blunted by prior alendronate therapy. Paired biopsies at baseline and after 24 months of TPTD from 29 ALN-pretreated (~5 yrs) and 16 untreated patients revealed the increase in activation frequency was 0.11-0.34 cycles per year in ALN and 0.19-0.33 with TPTD, while osteoid surfaces were 3.96-9.8% in the ALN-pretreated group and 6.2-11.3% in the untreated group. The increased level of formation is similar in patients who were either untreated or had lower bone turnover due to previous ALN. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Osteoporos Int 2010;21:2027-36
Misof et al paired transiliac bone biopsy before and after one year teriparatide in 16 women treated with alendronate (priorALN) or risedronate (priorRIS) for at least two years and then treated for 12 months with teriparatide. BMDD response to one year of teriparatide did not depend on the type of bisphosphonate. For priorALN patients increases in low mineralized bone areas (Cn.Ca(Low) +25.9%, Ct.Ca(Low) +62.0%, and Ct. heterogeneity of mineralization (Ct.Ca(Width) +22.8%). PriorRIS patients showed increased mineralization heterogeneity (Cn.Ca(Width) +14.8% and Ct.Ca(Width) +15.8%). J Bone Miner Res 2010;25:2297-303
Understanding the structural basis of a rise or lack of rise in BMD following antiresorptive therapy
Remodelling suppression with antiresorptive agents is thought of in terms of potency in suppressing remodelling, but the effects also depend on the remodelling that continues despite therapy. Calcium supplements suppress remodelling by about 10-20% so about 80% of the remodelling present before treatment continues. At the other extreme, denosumab reduces remodelling by about 80%, at least as measured using remodelling markers. When remodelling is suppressed, remodelling sites initiated before treatment complete remodelling with bone formation which reduces the existing intracortical porosity and focally fills excavated sites upon trabeculae and the endocortical surface (a change below the detection of most noninvasive methods). In addition, osteons that would be removed are not and continue to undergo secondary mineralization. So cortical vBMD increases for two reasons: the reduction in porosity and the increase in tissue mineral density of the osteons. The net effect also depends on the residual remodelling.
In the case of calcium supplementation 80% of the remodelling continues, so as the pores fill at the time of initiation of calcium, new porosity appears because the drug is a weak remodelling suppressant. Bone loss continues after a modest increase in BMD produced by the filling phase of resorption cavities present before treatment. This BMD increase is modest because of the appearance of almost as many new resorption sites as were present before treatment. With denosumab, only 20% of the remodelling sites present before treatment reappear during treatment so the filling phase of resorption sites present at the time of treatment occurs without being offset by new sites. The net effect of these changes on bone structure and tissue mineralization density varies depending on the drug used and on the baseline remodelling intensity in an individual.
Seeman et al reported that in 247 postmenopausal women randomized to denosumab, alendronate or placebo for 12 months, denosumab decreased serum C-telopeptide more rapidly and markedly than alendronate. Alendronate prevented the decline in total vBMD observed with placebo whereas denosumab prevented the decline or improved total and cortical vBMD. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p<0.001). J Bone Miner Res 2010;25:1886-94 The reason why denosumab improved cortical vBMD while alendronate only prevented the decrease can be understood from the above. With alendronate, remodelling suppression is about 50%. so the increase in tissue density produced by the remodelling suppression would increase cortical vBMD, but the continued remodelling reduces cortical density by removing osteons and leaving porosity.
Similar observations with alendronate were reported by Burghardt et al. During 24 months, alendronate prevented the decrease in distal tibia cortical vBMD seen in placebo but did not change cortical vBMD relative to baseline because the net effect of filling of resorption sites present before treatment plus secondary mineralization of osteons not removed (both of which increase cortical vBMD) what offset by the continued appearance of about 50% of remodelling sites which produce porosity. J Bone Miner Res 2010;25:2282-95
Zoledronate – is annual administration needed?
Grey et al report that the antiresorptive effects of a single 5 mg dose of zoledronate are sustained for 3 years in 50 postmenopausal women with osteopenia. Mean serum β-CTX and P1NP were 44% and 40% lower in the zoledronate group vs. placebo. BMD was higher in the zoledronate group than in the placebo group by 6.8% at the spine, 4.0% at the total hip, and 2.0% at the total body. Between-group differences in markers of bone turnover and BMD were stable from 12 to 36 months. J Bone Miner Res 2010;25:2251-5
Gamsjaeger et al analysed the biopsies (152 patients, 82 ZOL and 70 placebo) by Raman microspectroscopy. ZOL increased the mineral/matrix ratio. Mineral crystallites had carbonate content and maturity/crystallinity characteristics of younger bone, suggesting that ZOL may be exerting an effect on bone matrix formation in addition to its antiresorptive effect. J Bone Miner Res 2011;26:12-8
O'Neal et al reported that changes in architecture and matrix properties associated with alendronate reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage. Trabecular cores from the distal femur of beagle dogs treated for one year with alendronate subjected to uniaxial compression had 25% lower von Mises stress for trabeculae exhibiting severe and linear microcrack patterns, whereas there was no reduction for diffuse microdamage formation. Severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae. Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. Bone 2010;47:241-7
Kusamori et al developed a transdermal patch of alendronate. The maximum permeation fluxes through rat and human skin were 1.9 and 0.3 µg/cm2 per hour, respectively. The bioavailability (BA) in rats was 8.3% (patch) and 1.7% (oral) administration. The plasma calcium was reduced in 1α-hydroxyvitamin D3-induced hypercalcemia in rats. The alendronate patch also suppressed the decrease in bone mass in rats with osteoporosis. Modest alendronate-induced erythema of rat skin was observed. Incorporation of butylhydroxytoluene in the alendronate patch suppressed this alendronate-induced skin damage maintaining permeation and pharmacologic effects. J Bone Miner Res 2010;25:2582-91
Adverse events of bisphosphonates
Shane et al provide recommendations of a task force that the definition of atypical fracture requires the location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no trauma, a medial spike when the fracture is complete, and absence of comminution. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including bisphosphonates, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. J Bone Miner Res 2010;25:2267-94
Vestergaard et al studied users of bisphosphonates and other drugs (n=103,562) and three age- and gender-matched controls from the general population (n=310,683). After initiation of therapy, an increased risk of subtrochanteric fractures was seen for alendronate (HR=2.41, 95% CI 1.78-3.27), etidronate (HR=1.96, 95% CI 1.62-2.36), and clodronate (HR=20.0, 95% CI 1.94-205), not raloxifene (HR=1.06, 95% CI 0.34-3.32). An increased risk of subtrochanteric fractures was also present before alendronate (OR=2.36, 95% CI 2.05-2.72), etidronate (OR=3.05, 95% CI 2.59-3.58), clodronate (OR=10.8, 95% CI 1.14-103), raloxifene (OR=1.90, 95% CI 1.07-3.40), and strontium ranelate (OR=2.97, 95% CI 1.07-8.27). The authors suggest that not all subtrochanteric fractures are the result of treatment. Osteoporos Int 2011;22:993-1001
While prolonged therapy may increase the risk for atypical fractures, this risk is small and is probably much smaller than the risk of failure to treat or poor compliance with treatment. Imaz et al reported in a meta-analysis of five articles totalling 236,540 patients, followed for one year, had a pooled persistence of 184.09 days. The meta-analysis of five articles, totalling 234,737 patients, also followed for one year, provided a pooled medication possession ratio mean of 66.93%. The meta-analysis of six articles, totalling 171,063 patients, followed 1 and 2.5 years, provided a pooled 46% increased fracture risk in noncompliant patients vs. compliant patients. The increased fracture risk was 16% for nonvertebral, 28% for hip and 43% for clinical vertebral fractures. Osteoporos Int 2010;21:1943-51
Bisphosphonate therapy is associated with adverse events including ONJ. While no known treatment is available, in an experimental model in mice Kikuiri et al reported that zoledronate plus dexamethasone causes BRONJ-like in part by suppressing the adaptive regulatory T-cells and activating the inflammatory T-helper-producing interleukin 17 cells. Systemic infusion with mesenchymal stem cells prevented and cured BRONJ-like disease possibly via induction of peripheral tolerance. The suppressed Tregs/Th17 ratio in zoledronate- and dexamethasone-treated mice is restored in mice undergoing salvage therapy with Tregs. J Bone Miner Res 2010;25:1668-79
Allen et al studied female untreated beagle dogs (CON) or treated with intravenous zoledronic acid (ZOL). Following the extraction of the 4th premolars, initial infilling of the socket was not affected by ZOL, but subsequent removal of this bone was suppressed. After 8 weeks of healing, the alveolar cortical bone adjacent to the extraction socket had a remodelling rate 50% per year in CON animals while ZOL-treated animals had a rate of <1% per year. One ZOL-treated animal developed exposed bone post-extraction which eventually led to the formation of a sequestrum. Assessment of the sequestrum with µCT and histology showed that it had features consistent with those reported in humans with ONJ. Osteoporos Int 2011;22:693-702
DVT and drug therapy
Lamberg et al studied 4193 cased and 41,197 controls. 149 cases (3.6%) and 1078 controls (2.6%) were current bisphosphonate users. The adjusted OR for VTE among the current bisphosphonate users compared with nonusers was 1.03 (0.84-1.26), and when restricted to cases of unprovoked thromboembolism, the adjusted OR was 1.08 (95% CI 0.82-1.42). Osteoporos Int 2010;21:1911-7
Breart et al reported a greater prevalence of VTE in osteoporotic compared to nonosteoporotic patients, but not between persons with osteoporosis receiving treatment than those not receiving treatment, showing any greater association in treated patients with strontium ranelate or alendronate compared to untreated osteoporotic patients. In this study the authors reported there was an increased risk for VTE in untreated osteoporotic women vs. nonosteoporotic women (annual incidence 5.6 and 3.2 per 1000 patient-years, respectively; relative risk 1.75). The annual incidences of VTE in osteoporotic patients treated with strontium ranelate and alendronate were 7.0 and 7.2 per 1000 patient-years, respectively, with no significant difference between untreated and treated patients whatever the treatment. The sample size was large; 1546 untreated women, 20,084 treated with alendronate, 2408 patients treated with strontium ranelate and 115,009 nonosteoporotic women. Osteoporos Int 2010;21:1181-7 Well, large sample sizes in cohort studies do not solve the problem of potential bias in sampling. The point of a randomized trial is to control for covariates that might influence outcomes. In cohort studies such as this, it is not possible, even with the large sample sizes to exclude the possibility of confounding. The risk of VTE was reported in randomized trials of strontium ranelate and other drugs and this should be borne in mind.
Does taking a bisphosphonate prolong survival?
There are several studies that suggest this is so. Of course the study by Kyle et al of zoledronic acid following hip fracture demonstrated a 28% reduction in mortality unrelated to the prevention of fractures. Beaupre et al studied 220 hip fracture patients randomized to case manager or usual care. During 3 years, 101 (46%) patients started oral bisphosphonates and 65 (64%) remained on treatment. Overall, 24 (11%) patients died, 19 (9%) had new fractures, and 42 (20%) reached the composite outcome of death or fracture. Compared to no treatment, bisphosphonate exposure was associated with reduced mortality (17[16%] vs. 7[7%]; aHR=0.92 per month treated; 95%CI 0.88-0.97) and composite endpoints (28[26%] vs. 5[15%]; aHR=0.94 per month treated; 95%CI 0.91-0.97). Osteoporos Int 2011;22:983-91 The reasons for this association are not known. Whether this is a healthy user effect is one explanation.
Reid et al reported the results of iliac crest bone biopsies at 24 and/or 36 months from 45 women receiving placebo and 47 denosumab in the FREEDOM trial and at 12 months from women treated with alendronate in the STAND study (21 continuing alendronate and 15 changed to denosumab at trial entry). In the FREEDOM study, median eroded surface was reduced by >80% and osteoclasts were absent from >50% of biopsies. Double labelling in trabecular bone was observed in 94% of placebo and in 19% of denosumab treated subjects. Median bone formation rate was reduced by 97%. In the STAND trial, indices of bone turnover tended to be lower in the denosumab than alendronate group. Double labelling in trabecular bone was seen in 20% of the denosumab biopsies and in 90% of the alendronate samples. These findings reflect suppression of tissue level remodelling. What is needed is biopsies after stopping therapy or at the end of a treatment cycle. J Bone Miner Res 2010;25:2256-65
Genant et al reported that in 332 women with spine areal BMD T-scores between -1.0 and -2.5, denosumab 60 mg or placebo every 6 months during the 24-month study, increases in BMD were seen at the ultradistal region (4.7% [95% CI 3.6-5.7]; P<0.001) and total BMC (5.7% [95% CI 4.8-6.6]; P<0.001) over placebo. Cortical bone had increases in BMD, BMC, and thickness, and trabecular bone had an increase in BMD relative to placebo. Bone strength, estimated by density-weighted PMI, increased compared with placebo after 6 months, with the largest increase occurring at 24 months in the ultradistal region (6.6% [95% CI 5.6-7.6]; P<0.0001). Bone 2010;47:131-9
When teriparatide is administered, bone remodelling markers increase and then decrease despite continued administration. The significance of this observation is far from clear. Yu et al administered teriparatide either as a constant or an escalating subcutaneous dose (30 µg daily for 18 months or 20 µg daily for 6 months, then 30 µg daily for 6 months, and then 40 µg daily for 6 months). All markers differed between the two treatment groups. During the final six months, bone markers declined in the constant dose group but remained stable or increased in the escalating dose group. However, mean area under the curve did not differ between treatments for any marker, and BMD increases were equivalent. The mystery remains. Bone 2011;48:713-9
Sclerostin antibody
There are many unmet needs in therapeutics. One is the need for an anabolic agent that influences the periosteal and all three components of the endosteal envelope. Li et al reported that Scl-AbII increased areal BMD, improved trabecular and cortical architecture at L5, femoral diaphysis (FD), and femoral neck (FN), associated with a higher maximal load of L5, FD, and FN in the high-dose group. Mineralizing surface, mineral apposition rate and bone formation rate at the proximal tibial metaphysis and tibial shaft were greater on trabecular, periosteal, and endocortical surfaces in both Scl-AbII dose groups. What is interesting is that the drug, which inhibits sclerostin, an inhibitor of bone formation, also reduces bone resorption by mechanisms that are not understood. J Bone Miner Res 2010;25:2647-56
Tian et al reported that in rats treated with Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. for 4 weeks, both doses increased bone formation and trabecular bone volume and thickness and decreased resorption in the trabecular bone. Scl-AbIII decreased resorption and increased formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body. Bone 2010;47:529-33
Tian et al also reported that antibody-mediated blockade of sclerostin is a promising anabolic treatment for immobilization-induced osteopenia. Rats were normal weight-bearing (normal-loaded, NL) or right hindlimb-immobilized (under-loaded, UL were treated with Scl-Ab at 5 or 25 mg/kg for 4 weeks. UL rats had reduced body and muscle weights, increased marrow fat, increased trabecular bone resorption and periosteal mineral apposition rate (MAR) and decreased trabecular MAR and bone formation rate (BFR/BS). In NL bones, Scl-Ab increased bone formation and decreased bone resorption, resulting in increased trabecular and cortical bone mass. In UL trabecular bone, Scl-Ab at 5 or 25 mg/kg induced dose-dependent increases in trabecular bone volume and thickness, mineralized surfaces (MS/BS), MAR and BFR/BS, and a decrease in eroded surface (Er.S/BS) compared with UL controls. In UL cortical bone, Scl-Ab induced increases in cortical width, periosteal and endocortical MS/BS, MAR and BFR/BS, and decreases in endocortical Er.S/BS compared with UL controls. Bone 2011;48:197-201
Padhi et al repoted a randomized, double-blind, placebo-controlled, ascending, single-dose study, 72 healthy subjects received AMG 785 or placebo (3:1) subcutaneously (0.1, 0.3, 1, 3, 5, or 10 mg/kg) or intravenously (1 or 5 mg/kg). One treatment-related serious adverse event of nonspecific hepatitis was reported and resolved. AMG 785 pharmacokinetics were nonlinear with dose. Dose-related increases in formation markers and decrease in sCTx occurred. In addition, increases in BMD of up to 5.3% at the spine and 2.8% at the total hip compared with placebo were observed on day 85. Six subjects in the higher-dose groups developed anti-AMG 785 antibodies, two of which were neutralizing, with no effect on the pharmacokinetics or pharmacodynamics. This drug is a promising agent in osteoporosis treatment. J Bone Miner Res 2011;26:19-26
Cat on a hot tin roof
Cathepsin K inhibitors prevent resorption of bone by blocking the degradation of collagen. Unlike denosumab, the osteoclast numbers are not reduced, so that if there are products of the osteoclast that are important in promoting bone formation, the great hope is coupling with reduction in resorption but continued bone formation at the cellular level. Eisman et al studied postmenopausal women with BMD T-scores between -2.0 and -3.5 who received placebo or ODN 3, 10, 25, or 50 mg weekly. After 2 years, patients (n=189) were rerandomized to ODN 50 mg weekly or placebo for an additional year. Continued treatment with 50 mg of ODN for 3 years produced increases from baseline and from year 2 in BMD at the spine (7.9% and 2.3%) and total hip (5.8% and 2.4%). Urine NTx remained suppressed at year 3 (-50.5%), but bone-specific alkaline phosphatase (BSAP) was unchanged from baseline. Treatment discontinuation resulted in bone loss at all sites, but BMD remained at or above baseline. After ODN discontinuation at month 24, turnover markers increased above baseline but resolved by month 36. J Bone Miner Res 2011;26:242-51
Pennypacker et al compared two cathepsin K inhibitors (CatKIs) with ALN in OVX rabbits. OVX demonstrated loss (9.8% to 12.8%) in lumbar vertebral (LV) BMD at 13-weeks prevented by estrogen or ALN. L-006235 (L-235), at 10 mg/kg per day for 27 weeks, decreased LV BMD loss. ALN reduced spine cancellous mineralizing surface by 70%, L-235 had no effect. Endocortical bone formation rate and the number of double-labelled Haversian canals in the femoral diaphysis were not affected by L-235. ODN 4 or 9 µM/day for 27 weeks prevented LV BMD loss vs. OVX-vehicle control comparable with sham or ALN. ODN also dose-dependently increased proximal femur, femoral neck, and trochanter BMD. ODN did not reduce bone formation at any sites. Although CatKIs had similar efficacy to ALN in preventing bone loss in adult OVX rabbits, this novel class of antiresorptives differs from ALN by sparing bone formation. J Bone Miner Res 2011;26:252-62
Strontium ranelate
Strontium ranelate has established antifracture efficacy in human subjects. In this study, Geoffroy et al examined the effects of this drug on fracture incidence in mice overexpressing Runx2, a model of osteopenia associated with vertebral fractures. Treatment resulted in fewer fractures (-60%, p<0.05). In lumbar vertebrae, strontium ranelate improved resistance to compressive loading (ultimate force, +120%, p<0.05). What is a mystery with this drug is the mode of action. The authors report higher trabecular bone volume and trabecular number, lower trabecular separation and higher cortical thickness (+17%, p<0.05) and reduced marrow cavity cross section. These observations are based on histomorphometry and do support the notion of an anabolic effect. What is missing in the data is more detail about the growth rate differences in the animals and whether this was no different. If so, this would be the first histological evidence to support the claims of an anabolic effect. I reserve my interpretation for now and still favour the notion that the strength improvement is due to an effect on the material properties of bone. Osteoporos Int 2011;22:289-97
TGFβ antibody
Edwards et al report that an antibody (1D11) directed at all three isoforms of TGFβ increased BMD, trabecular thickness, and bone volume by up to 54%, accompanied by elevated osteoblast numbers and decreased osteoclasts. Biomechanical properties of bone also were enhanced with increased bending strength and tissue-level modulus with an 11% increase in the mineral-to-collagen ratio of trabecular bone. J Bone Miner Res 2010;25:2419-26
The tyrosine kinase inhibitor
Vandyke et al report that dasatinib is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia. It inhibits M-CSF receptor c-fms, osteoclast formation and activity in vitro. Sprague Dawley rats administered dasatinib (5 mg/kg/day) or vehicle by gavage or ZOL (100 µg/kg/6 weeks) subcutaneously were followed 12 weeks. Whole body BMD and tibial cortical thickness where unchanged in the dasatinib- or ZOL-treated animals relative to controls. However, µCT analysis of cancellous bone at the proximal tibias showed that trabecular BV/TV and Tb.Th increased comparable with ZOL-treated group. These changes were associated with a decrease in osteoclast numbers (N.Oc/B.Pm) and surface (Oc.S/BS) and decreased serum levels of the CTX-1. MAR, BFR, osteocalcin and P1NP were not altered. J Bone Miner Res 2010;25:1759-70
What do vitamin D, snake oil, and bloodletting have in common?
Lack of evidence, that's what. If randomized trials were properly designed and executed, we would not need meta-analyses. It is almost without exception, and I can't think of an exception, all studies of calcium alone, vitamin D alone or combinations of both are plagued by serious issues in design and execution. The design flaw is that most, if not all the studies, were carried out in persons who were neither calcium nor vitamin D deficient. The two flaws in execution are dropouts and poor compliance, usually about 50% for each. If patients are not deficient in calcium and vitamin D. how can the effect of deficiency on fracture rates be determined and how can the effect of correction on whatever the consequence may be ascertained?
The answer submitted is subgroup analysis. This is problematic also if we adhere to the notion that the randomized trial is the best level of evidence we can make inferences from because covariates influencing outcomes are likely to be evenly distributed in both groups provided the sample size is large enough. Once a subgroup analysis is done, whether this is a subgroup of 'low' calcium intake group or compliers to therapy, randomization may be violated – the operative word is "may be" and that should be enough if we are rigorous. Without this, the independent effects of both known and unknown covariates influencing fracture rates cannot be excluded; that's it! If we deviate from this requirement we may as well ask the opinion of the next door neighbour.
Healthy users of placebo have better outcomes than noncompliers to placebo, so it is possible that any benefit of calcium or vitamin D in compliers reflects this effect rather than the effect of treatment. This problem exists with dose finding as well. The claim that a dose of 800 U vitamin D, but not 400 U vitamin D, is the correct dose has never been tested in a randomized trial of patients selected on being vitamin D deficient randomized to placebo, 400 U, 800 U with fracture outcomes assessed prospectively. The argument that it is unethical to give placebo begs the question, it may be argued that it is unethical not to give placebo if we don't know and the sample size requirements to detect a better fracture risk reduction with 800 U over 400 U is likely to be formidable.
Bischoff-Ferrari et al report the results of a meta-analysis of double-blind randomized control trials, 8 examining falls (n=2426) and 12 examining nonvertebral fractures (n=42,279). Benefits were observed at 700 to 1000 IU vitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30-44 ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested benefits with the highest 25(OH)D evaluated (median between 75 and 110 nmol/l). Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1800 to 4000 IU vitamin D per day without risk. Well, should we then proceed with these doses? Osteoporos Int 2010;21:1121-32.
Salovaara et al reported that among women aged 65-71 years, 1586 in the intervention group given 800 U vitamin D plus 1 g calcium, and 1609 in the control group. None of the effects reached statistical significance. During 3 years the risk of any fracture decreased by 17% [aHR=0.83; 0.61-1.12], nonvertebral fracture decreased by 13% (aHR=0.87; 0.63-1.19), distal forearm fractures decreased by 30% (aHR=0.70; 0.41-1.20), any upper extremity fractures decreased by 25% (aHR=0.75; 95% CI 0.49-1.16), lower extremity fractures (aHR=1.02; 0.58-1.80). J Bone Miner Res 2010;25:1487-95
Cummings et al reported that in women aged 60-85 years with osteoporosis or a vertebral fracture, and women with low bone mass were assigned to arzoxifene 20 mg or placebo daily. After 3 years, the incidence of vertebral fractures in patients with osteoporosis was 2.3% lower in the arzoxifene group than in the placebo group, a 41% relative risk reduction (0.45-0.77). In the overall population, the cumulative incidence of invasive breast cancer over 4 years was reduced by 1.3%, with a 56% relative reduction in risk (HR 0.44, 0.26-0.76); there was no significant decrease in nonvertebral fracture risk. Arzoxifene increased the cumulative incidence of venous thromboembolic events by 0.7%, with a 2.3-fold relative increase (95% CI 1.5-3.7). J Bone Miner Res 2011;26:397-404
Ivergard et al estimated costs and benefits of 5-year raloxifene based on 10-year fracture probability estimated with FRAX® below 20% and 5-year invasive breast cancer risk of 1-5%. The cost per QALY gained ranged from US $22,000 in women age 55 with 5% invasive breast cancer risk and 15-19.9% fracture probability, to $110,000 in women age 55 with 1% invasive breast cancer risk and 5-9.9% fracture probability. At lower fracture risk with lower cancer risk, the cost-effectiveness of raloxifene worsened. At fracture risk of 15-19.9% raloxifene was cost-effective also in women at lower invasive breast cancer risk. The cost-effectiveness is contingent on their 5-year invasive breast cancer risk. Bone 2010;47:966-74
Note from the Editor
The purpose of Progress in Osteoporosis is to provide the reader with a summary of the most important literature published in the preceding three to four months in the field of osteoporosis. Most reviews and original research are cited. In addition, summaries and figures are provided for readers who may not have easy access to all the specialist literature. The summaries are based on the contents of abstracts, which have been abbreviated to concisely convey the main theme. The contents of the abstracts and figures should be used only as a means of directing the reader to the original literature and should not be quoted verbatim or cited as a reference. The opinions expressed in the Overview are my own and do not necessarily reflect those of the International Osteoporosis Foundation.


text:
By Rob Kiser
Piqua Daily Call
PIQUA — The Piqua football team needed a big win over Xenia Friday night at Alexander Stadium/Purk Field to right the ship.
Instead the 6-1 Bucs scored on their first three possessions without throwing a pass and held on for a 21-7 victory in MVL action. The loss dropped Piqua to 3-4 on the season.
On the opening drive, Xenia went 80 yards in 11 plays.
Quarterback Brett Russell had an 13-yard run on the drive, Andrew Pollender had a 11-yard run and Kevin Johnson had a 14-yard run, before running 15 yards for a touchdown. Hayden Falvey's PAT kick made it 7-0 with 7:08 remaining in the opening quarter.
After a Piqua three-and-out, Xenia went 57 yards in 10 plays.
Pollender had a 15-yard run on a second-and-nine play and Mickey Penewit would score on a 5-yard run. Falvey's PAT kick made it 14-0 in the final minute of the first quarter.
The Indians got a first down on its next drive, before Falvey recovered a fumble at the Piqua 37-yard line.
It took just four plays for Xenia to get in the end zone, with Johnson running it in from 21 yards out. Falvey's kick made it 21-0 with 8:10 remaining in the half.
Piqua then put a drive together.
Jasiah Medley had a 10-yard run and Jerell Lewis had a 15-yard run, but Piqua had to punt from the Xenia 31 and the half ended with Xenia leading 21-0.
The momentum swung immediately in the second half.
Piqua went 64 yards in 14 plays with the second half kickoff to cut into the deficit.
Tight end Caleb Lyons caught a 13-yard pass from Blane Ouhl on a third-and-eight to convert a first down.
Ca'ron Coleman would finish the drive with a 10-yard run for the touchdown and Jackson Trombley's kick had Piqua within 21-7 with 7:02 remaining in the third quarter.
Xenia started on its own 16 on its next drive and drove inside the Piqua 20, before Makeegen Kuhn recovered a fumble at the Piqua 17-yard line.
Medley had a 21-yard run to moved the ball into Xenia territory, but on fourth-and-five, Piqua came up inches short of a first down.
Piqua forced a three-and-out and got the ball back with 3:53 remaining at its own 37-yard line.
Medley had a 15-yard run for one first down and Ouhl connected with Keegan Patton for 13 yards and another first down before the drive stalled out.
Xenia picked up two first downs and ran the clock out.
Pollender led the Xenia rushing attack with 145 yards on 19 carries, while Johnson had 82 yards and 11 carries.
Medley had eight carries for 53 yards for Piqua, while Coleman had 10 carries for 47 yards.
Ouhl had 29 yards passing.
Piqua will be back in action Friday, hosting Greenville.
Contact Piqua Daily Call Sports Editor Rob Kiser at firstname.lastname@example.com.
©2019 Miami Valley Today, all rights reserved.


text:
The 2018 Courier Journal Sports Awards Special Olympics Athlete of the Year Award winner is Aaron Coomes from Waggener High School! Louisville Courier Journal
Waggener's Aaron Coomes was named the Boys Special Olympics Athlete of the Year at Thursday night's Courier Journal Sports Awards presented by Kroger at the Louisville Palace.
Coomes has been a Special Olympics athlete for seven years and has excelled in swimming, basketball, softball and skiing. He competes for the Wildcats' Unified basketball and track teams and has been recognized as a great teammate.
The Courier Journal Sports Awards recognize the best in Kentuckiana high school athletics. For more coverage from Thursday's awards ceremony, visit courier-journal.com/sportsawards.


text:
Chisel Plough
- Works deep beneath the surface. Ideal when topsoil is fertile but subsoil is not productive.
- Shatters the soil well below the surface.
- Does not invert of turn the soil, causing limited soil distribution.
- Loosen and aerate soil, leaving crop residue at top of soil.
- Reduces the effect of Compaction.
- Help increasing water storage capacity.
- Help break-up hardpan.
- More tractor power required per shank. (10-15HP)
- Removing the side shanks turns this implement into a sub soiler.
- Replaceable Shanks/Points.


text:
This post may contain affiliate links. Please read my disclosure and privacy policy.
Flax "eggs" are an easy vegan egg substitute. They're a great baking alternative for vegans and for those who have allergies and must follow an egg-free diet.
My Favorite Vegan Egg Substitute
You can make this vegan egg substitute using flax seeds or chia seeds. I think chia seeds provide the most neutral flavor when compared to flax seeds, but ground golden flax seeds (pictured above) might visually blend into baked goods a bit better.
Because they are so similar, I'll use ground chia or flax "eggs" interchangeably in recipes, depending on whichever is most convenient in my pantry.
How to Make a Flax Egg or Chia Egg
To prepare a flax or chia egg, simply grind the seeds in a coffee grinder. It's not uncommon to find bags of already ground flax seeds at the grocery store now (I've seen them at Trader Joe's and Costco) so you maybe able to skip this step if you buy it pre-ground.
Chia seeds ground in my coffee grinder
To Make One Flax Egg combine:
- 1 tablespoon of ground seed (measure after grinding!)
- 3 tablespoons of water
Stir well, and allow the mixture to set for about 10 minutes.
After 10 minutes or so, the result should be a sticky egg-like substitute, with a gelatinous, stretchy texture.
How To Make Flax Eggs (or Chia Eggs)
- 1 tablespoon ground flax or chia seeds
- 3 tablespoons water
- Whisk together the ground seeds and water until well combined, then place in the fridge to set for 15 minutes.
- Use as you would an egg in many of your favorite baking recipes.
Per egg: Calories: 58, Fat: 3g, Carbohydrates: 5g, Fiber: 4g, Protein: 1g
How do you use Flax Eggs in baking?
In recipes that call for just 1 or 2 eggs, a flax or chia egg can usually replace regular eggs– especially in recipes that call for all purpose or whole wheat flour.
If recipes call for more than 2 eggs, chia and flax eggs will not produce the best results. The center is usually more gooey and will not rise the way a recipe made with real eggs would. I would not use this vegan egg substitute in recipes calling for coconut flour, or in any sort of soufflé recipe.
Which recipes call for flax and chia eggs?
- Vegan Almond Butter Brownies
- Vegan Baked Banana Oatmeal Cups
- Vegan Flourless Peanut Butter Temptations
- Date-Sweetened Vegan Peanut Butter Cookies
I hope this tutorial helps you with your egg-free and vegan baking endeavors! If you try this recipe, please leave a comment below letting me know how it works out for you.
Reader Feedback: What's your favorite recipe to use flax eggs or chia eggs in?


text:
Layer Slider Plugin – Web Settler
For elegant and professional WordPress slidersSlider Plugin is a multi purpose slider for creating Image sliders,Content sliders, and mind blowing slideshows with stunning effects. It uses modern technologies to provide the smoothest experience that's possible. It has beautiful & easy to use visual drag & drop slider builder with realtime preview. It supports beautiful and … Read more Layer Slider Plugin – Web Settler
To access MetaSyst data, you must be logged in.


text:
Even though Australia abandoned the 457 visa subclass, it doesn't mean that the country is not suffering from a skill shortage. Australia is firm on the fact that it doesn't require immigrants but only want highly skilled immigrants. So the new high talent visa that the country is developing will be only for foreign talent that found a job offer paying them AU $180,000 per annum. The visa will have two sets of eligibility - one for the foreign candidate and another of Australian employer. It clearly isn't for startups because companies need to have an annual turnover of at least $4 million and must belong to fields like biomedicine and agriculture technology. However, if startups fulfill the annual turnover criterion, they can apply for the visa despite not belonging to the two mentioned fields. Three new work permits replaced the 457 visa subclass at the beginning of 2018, which are categorized according to skills set and earnings. The newly proposed visa will work along with these three work permits, and its trial will begin in July 2018, before which all eligible companies will go through a two-month consultation period. Times are changing in Australia since the choice of foreign employees is changing from the United States and the United Kingdom to India and China. The visa provides a direct path to permanent residency, which the employee will get after living in Australia for three years.
Hi! How can we help you?
Click below button to start chat


text:
Follow The Entrepreneur
A leading investor summit which for the first time relocated to Malta, bringing together leading businesses, investment firms and entrepreneurs.
Learn More
The Goal
To build Follow The Entrepreneurs online presence through a multi-channel marketing strategy that influenced entrepreneurs, businesses and investment firms to attend the summit in Malta.
Digital Marketing Services
– Content Marketing
– Website design
– Targeted advertising
– Social media marketing
– Video marketing
– Analysis & Strategy
– Brand development
– Consultancy and training
Client Testimonial
"I can not recommend Growth Gurus digital marketing highly enough. They came on board, owned this project and really delivered incredible results!" (See portfolio)."


text:
Our vast selection of pre-owned vehicles gives you plenty of options when looking for a new car, truck, van, or SUV on a budget. Pennsylvania and New Jersey drivers near Trenton, Hamilton, Princeton, and Morrisville PA can visit Davis Hyundai in Ewing to explore our selection of used vehicles at great discounts.
With some vehicles starting at and below $10,000, we are sure you can find a quality used vehicle that fits your personal budget. In addition to our Hyundai models, drivers can discover a wide selection of sedans from Ford, Honda, and Toyota. Visit our dealership in Ewing today or call us directly at (888) 712-4690 to speak directly with our Sales professionals. Come by to get behind the wheel for a test drive soon!
Our Service Center is equipped with the latest technology, factory parts, and accessories to keep your vehicle running smoothly. Schedule your next service appointment with us to see why drivers keep coming back to Davis Hyundai.
We offer shuttle service and loaner cars so you can keep going while your vehicle is in the shop. Our dealership is open Monday through Saturday so you can stop by after work or on the weekend. Our expert technicians can address your routine maintenance needs or repairs as well as keep the costs low with our selection of coupons and rebates.
At Davis Hyundai, we work to create a positive experience for our drivers when they're searching for a new vehicle. Our Finance Center staff works with you to navigate our multiple auto financing options to determine which option would be best for you. Whether you're looking to purchase, lease, or apply for a loan, our finance professionals can discuss the benefits of each.
Contact or visit us today to discuss our current finance specials, our finance application process, determine your possible trade-in value, and more.
All vehicle specifications, prices and equipment are subject to change without notice. See above for information on purchase financing and lease program expiration dates. Prices and payments (including the amount down payment) do not include tax, titles, tags, or other fees required by law or lending organizations. The estimated payments may not include upfront finance charges that must be paid to be eligible for the purchase financing program used to estimate the APR and payments. Listed Annual Percentage Rates are provided for the selected purchase financing or lease programs available on the current date. Program expiration dates reflect currently announced program end dates, but these programs are subject to change at any time.


text:
Torrance, California is a coastal community with 1.5 miles of shore-front beaches, which are less well known than others by tourists to the area. It is a moderately sized city with warm, California sunshine, luscious parks and shopping at Del Amo Fashion Center – one of the five largest malls in the country.
Nothing goes better with sand, sun and shopping than smooth skin, and LaserAway in nearby Marina Del Rey is ready to give you the look and feel hair-free skin you've always wanted but maybe never thought you could afford. LaserAway offers the latest state-of-the-art laser hair removal in a clean, comfortable spa-like environment. Laser hair removal allows you to rid your body of unwanted body hair without the worry of razor nicks or uncomfortable rashes of shaving and waxing. Plus, salt and sand don't exactly go with razor burn.
LaserAway also uses cutting-edge technology to help treat sun damage, which is common in Torrance and surround Southern California. Spending the day at the beach multiple times a year without proper coverage and sunscreen can lead to a number of skin issues, which LaserAway is equipped to address. LaserAway offers full medical spa services, including Microdermabrasion, Facials, Photofacials and skin aging treatments.
Keep your skin smooth and looking the way you want it to without having to deprive yourself of the fun that awaits you in Torrance. Take advantage of a free, first-time consultation to discuss the many services LaserAway has to offer and see just how affordable looking your best can be. Stop wasting time in your bathroom shaving and waxing when you could be lounging in the sun. Let LaserAway give you the look you deserve for less money and effort than you ever thought possible. Spend your days in Torrance the way you want to – in a permanent state of vacation.