The goal of treatment is to reduce bone pain and stabilize or prevent other problems such as progressive deformity, fractures, hearing loss, high-output cardiac failure, and immobilization hypercalcemia. Calcitonin and bisphosphonates are the first-line agents for this disease. Calcitonin is administered subcutaneously or intramuscularly in doses of 50–100 MRC (Medical Research Council) units every day or every other day. Nasal inhalation at 200–400 units/d is also effective. Higher or more frequent doses have been advocated when this initial regimen is ineffective. Improvement in bone pain and reduction in serum alkaline phosphatase and urine hydroxyproline levels require weeks to months. Often a patient who responds well initially loses the response to calcitonin. This refractoriness is not correlated with the development of antibodies.
Sodium etidronate, alendronate, risedronate, and tiludronate are the bisphosphonates currently approved for clinical use in Paget’s disease of bone in the United States. Other bisphosphonates, including pamidronate, are being used in other countries. The recommended doses of bisphosphonates are etidronate, 5 mg/kg per day; alendronate, 40 mg/d; risedronate, 30 mg/d; and tiludronate, 400 mg/d. Long-term remission (months to years) may be expected in patients who respond to a bisphosphonate. Treatment should not exceed 6 months per course but can be repeated after
VITAMIN D, METABOLITES, ANALOGS 6 months if necessary. The principal toxicity of etidronate is the development of osteomalacia and an increased incidence of fractures when the dosage is raised substantially above 5 mg/kg per day. The newer bisphosphonates such as risedronate and alendronate do not share this adverse effect. Some patients treated with etidronate develop bone pain similar in nature to the bone pain of osteomalacia. This subsides after stopping the drug. The principal adverse effect of alendronate and the newer bisphosphonates is gastric irritation when used at these high doses. This is reversible on cessation of the drug.
Patients with short bowel syndromes and associated fat malabsorption can present with renal stones composed of calcium and oxalate. Such patients characteristically have normal or low urine calcium levels but elevated urine oxalate levels. The reasons for the development of oxaluria in such patients are thought to be twofold: first, in the intestinal lumen, calcium (which is now bound to fat) fails to bind oxalate and no longer prevents its absorption; second, enteric flora, acting on the increased supply of nutrients reaching the colon, produce larger amounts of oxalate. Although one would ordinarily avoid treating a patient with calcium oxalate stones with calcium supplementation, this is precisely what is done in patients with enteric oxaluria. The increased intestinal calcium binds the excess oxalate and prevents its absorption. Calcium carbonate (1–2 g) can be given daily in divided doses, with careful monitoring of urinary calcium and oxalate to be certain that urinary oxalate falls without a dangerous increase in urinary calcium.
VITAMIN D, METABOLITES, AND ANALOGS
Calcifediol (25(OH)D3) Rayaldee Oral: solution Fleet Phospho-soda, K-Phos-Neutral, Neutra-Phos, Neutra-
Oral Generic, Rocaltrol
Phos-K Cholecalciferol (D3) Generic, Delta-D
Sevelamer carbonate or HCl Renagel, Renvela
BISPHOSPHONATES Alendronate sodium Generic, Fosamax
Doxercalciferol Generic, Hectorol
Ergocalciferol (D2) (vitamin Generic, Drisdol, others D2, calciferol)
Etidronate disodium Generic, Didronel