musculoskeletal and connective tissue disorders
Osteoporosis
Treatment of Osteoporosis
Risk factor modification Calcium andvitamin Dsupplements Antiresorptive medications (eg, bisphosphonates, hormone replacement therapy, a selectiveestrogenreceptor modulator, receptor activator of nuclear factor kappa-B ligand [RANKL] inhibitor [denosumab]) Anabolic agents (eg,parathyroid hormone(PTH) analogues such asteriparatideandabaloparatide) Romosozumab, a monoclonal antibody against sclerostin with both antiresorptive and anabolic effects The goals of treatment of osteoporosis are to preserve bone mass, prevent fractures, decrease pain, and maintain function. The rate of bone loss can be slowed with pharmacotherapy, but adequate calcium andvitamin Dingestion and physical activity are critical to maintaining optimal bone mineral density. Modifiable risk factors should also be addressed. Risk factor modifications aim to reduce risk of osteoporosis and risk of fractures. Measures include Doing weight-bearing exercise Moderating alcohol intake Smoking Cessation None Fall prevention measures Weight-bearing exercise can help increase bone mineral density ( Treatment references ). The optimal amount of weight-bearing exercise is not established, but an average of 30 minutes a day is recommended ( Clinicians should routinely ask about recent falls and otherwise Evaluation . Many older patients are at risk of falls because of poor coordination and balance, poor vision, muscle weakness, confusion, and use of is better absorbed in patients with achlorhydria, but both are well absorbed when taken with meals. Patients taking gastric acid suppressants (eg, proton pump inhibitors, H2 blockers) or those who have had Metabolic and Bariatric Surgery should take Vitamin Dsupplementationwith 600 to 800 units a day is recommended. Patients withvitamin Ddeficiency may need even higher doses. Supplementalvitamin Dis usually given as cholecalciferol, the natural form ofvitamin D, although ergocalciferol, the synthetic plant-derived form, is also acceptable. The 25-hydroxyvitamin Dlevel should be ≥ 30 ng/mL. are first-line therapy. By inhibiting bone resorption, bisphosphonates preserve bone mass and can decrease vertebral and hip fractures by up to 50% ( Treatment references ). Bone turnover is reduced after 3 months of bisphosphonate therapy and fracture risk reduction is evident as early as 1 year after beginning therapy. Bisphosphonates can be given orally or IV. Bisphosphonates include the following: for 3 years; however, a longer treatment duration may be warranted in some patients at particularly high fracture risk ( Treatment references ). Oral bisphosphonates must be taken on an empty stomach with a full (8-oz, 250 mL) glass of water. After administration, the patient must remain upright for at least 30 minutes (60 minutes foribandronate) and not take anything else by mouth during this time period, because food decreases bioavailability. These medications are safe to use in patients with a creatinine clearance > 35 mL/minute. Oral bisphosphonates can cause esophageal irritation. Esophageal disorders that delay transit time and symptoms of upper gastrointestinal disorders are relative contraindications to oral bisphosphonates. IV bisphosphonates are indicated if a patient is unable to tolerate or is nonadherent with oral bisphosphonates. Medication-Related Osteonecrosis of the Jaw (MRONJ) and atypical femoral fractures have been rarely reported in patients receiving antiresorptive therapy with bisphosphonates, Long-term bisphosphonate use may increase the risk of atypical femoral fractures ( Treatment references ). These fractures occur in the mid-shaft of the femur with minimal or no trauma and may be preceded by weeks or months of thigh pain. The fractures may be bilateral even if symptoms are only unilateral. To minimize fracture incidence, consideration should be given to stopping bisphosphonates after about 3 to 5 years of use in patients with osteoporosis (by DXA scan) but few or no other Risk Factors (3 years for IV 5 to 10 years of use in patients with osteoporosis (by DXA scan) and fractures or additional significant ongoing risk factors for bone loss and future fractures ( Treatment references , Intermittent cessation of bisphosphonate treatment (drug holiday), as well as initiation and duration of therapy, depend on patient risk factors such as age, comorbidities, prior fracture history, DXA scan results, and fall risk. The drug holiday is 1 year or longer. Patients on a bisphosphonate holiday should be closely monitored for a new fracture or accelerated bone loss evident on a DXA scan, especially after being off therapy for 2 years or more. During therapy with an antiresorptive medication such as a bisphosphonate, bone turnover is suppressed, as evidenced by low serum or urinary levels of (fasting) N-telopeptide cross-links (NTX) or C-telopeptide cross-links (CTX). Thus, measures of bone turnover markers can help determine adherence to therapy, as well as sufficient absorption, which are particularly useful for monitoring in patients taking oral bisphosphonates. These markers may remain low for ≥ 2 years off therapy. In untreated patients, an increase in levels of bone turnover markers, particularly with higher levels, indicates an increased risk of fracture. However, it is not clear whether levels of bone turnover markers should be used as criteria for when to start or end a drug holiday. The immediate initiation of a bisphosphonate after an osteoporotic fracture has been controversial because of a theoretical concern that these agents may impede bone healing. However, most experts recommend starting a bisphosphonate during the hospitalization for the fracture ( Treatment references ). There is no reason to delay therapy in order to obtain a DXA scan because a hip or vertebral fragility fracture establishes the presence of osteoporosis. is a monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL) and reduces bone resorption by inhibiting osteoclast formation ( Treatment references ). undergo a drug holiday because discontinuation may cause a rapid loss in bone mineral density and, importantly, increase the risk of fractures, particularly vertebral fractures, often multiple ( Treatment references ). If and when receptor modulator ( Selective estrogen receptor modulators (SERMs) ) that may be appropriate for treatment of osteoporosis in women who cannot take bisphosphonates or (see Menopausal Hormone Therapy ). However, taking a combination of a progestin and may provide short-term analgesia after an acute fracture, such as a painful vertebral fracture, due to an endorphin effect ( Treatment references ). It has not been shown to reduce fractures. (synthetic PTH [PTH1-34]) ( Treatment references ) and These three anabolic agents (teriparatide,abaloparatide, andromosozumab) are generally indicated for patients who have the following characteristics: Cannot tolerate antiresorptive medications or have contraindications to their use Fail to respond (ie, develop new fractures or lose bone mineral density) to antiresorptive medication, as well as calcium,vitamin D, and exercise Possibly have severe osteoporosis (eg, T-score<-3.0) or multiple vertebral fragility fractures Have glucocorticoid-induced osteoporosis (teriparatideonly) Any of these three anabolic agents can be considered for use during a bisphosphonate holiday. The use of anabolic agents to treat osteoporosis had been limited to 2 years based on a boxed warning because of concern of increased risk of developing Osteosarcoma (osteogenic sarcoma) in initial 2-year clinical trials, but the restriction of 2 years of therapy is no longer required. Consequently, although 2 years of treatment with an anabolic agent remains a reasonable course of therapy, giving a second 2-year course of therapy can now be considered. However, after completion of a treatment course with an anabolic agent, the bone mineral density gains are quickly lost if a patient is not quickly transitioned to an antiresorptive agent such as a Anabolic agents are safe to initiate at any time after a fracture. It is not clear whether early post-fracture use of anabolic agents accelerates bone healing. is a monoclonal antibody against sclerostin (a small protein made by osteocytes that inhibits new bone formation by osteoblasts). It has both antiresorptive and anabolic effects and has been shown to increase bone mineral density in the hip and lumbar spine and reduce fracture risk in postmenopausal women ( Treatment references ). for 2 years ( Treatment references ), and Monitoring for ongoing bone loss or the response to treatment with serial DXA scans should be done using the same DXA machine, and the comparison should use actual bone mineral density (g/cm2) rather than T-score. In patients with osteopenia, DXA should be repeated periodically to determine whether there is ongoing bone loss or development of frank osteoporosis requiring treatment. The frequency for follow-up DXA scanning varies from patient to patient, but some reasonable guidelines are as follows: Patients being treated with oral bisphosphonates: Repeat DXA scan usually after 2 to 3 years of therapy. DXA scan may be repeated more frequently if clinically warranted, for example in a patient taking corticosteroids. Patients treated with IV bisphosphonates: Repeat DXA scan for monitoring after 3 years of therapy to help determine if treatment has been adequate or a longer therapy course is warranted. Patients treated with anabolic therapy: Repeat DXA scan upon completion of therapy (18 to 24 months ofteriparatideorabaloparatide, 1 year ofromosozumab) to document improvement in bone mineral density with anabolic therapy and to establish a new baseline. Results may help identify patients at higher risk of fractures due to a suboptimal response to osteoporosis treatment. Patients who have a significantly lower bone mineral density despite treatment, or those who fracture while on treatment, should be evaluated for secondary causes of bone loss, poor medication absorption (if taking an oral bisphosphonate), and (except for patients treated with IV bisphosphonates or parenteral medications given in the office) medication adherence. Acute back pain resulting from a vertebral compression fracture can be treated with short-term orthopedic bracing as needed, analgesics, and, when muscle spasm is prominent, Heat and In some patients, vertebroplasty or kyphoplasty can be used to relieve severe pain due to a new vertebral fragility fracture; however, the evidence for efficacy is inconclusive ( Treatment references , 1.Howe TE, Shea B, Dawson LJ, et al: Exercise for preventing and treating osteoporosis in postmenopausal women.Cochrane Database Syst Rev(7):CD000333, 2011. 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