Osteoporosis antiresorptive therapy

Stepan JJ, Alenfeld F, Boivin G, Feyen JH, Lakatos P (2003) Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis. Endocr Regul 37 225-238... 

Treatment of osteoporosis depends on the cause. In secondary osteoporosis, treatment is directed at the underlying condition. Most therapies for the treatment of postmenopausal osteoporosis are directed at decreasing osteoclastic bone resorption. Antiresorptive therapies include bisphosphoiiates (alendronate and risedronate), estrogen replacement, selective estrogen receptor modulators (raloxifene), and calcitonin (nasal spray or injection). The FDA has recently approved recombinant hPTH(l-34) (injection), the first approved therapy for stimulating bone formation. 

Reviews A review of antiresorptive therapies for osteoporosis identified the following as the most commonly reported adverse effects of calcitonin therapy irritation of the nasal passage nasal mucosal erythema and minor bleeding sneezing rhinitis and nausea [3 ]. Across studies these side effects generally occurred in less than 10% of patients receiving calcitonin treatment. 

Chen JS, Sambrook PN. Antiresorptive therapies for osteoporosis a clinical overview. Nature Reviews Endocrinology 2012 8(2) 81-91. 

In contrast to many bone diseases, osteoporosis is often characterized by modest alterations in bone turnover, and thus only small changes may occur during therapy. A period of 1 to 3 years must pass before measurements of bone mass (for example, dual energy x-ray absorptiometry) can identify statistically significant changes in bone mass during therapy. Measurements of bone markers provide earlier assessments of bone resorption and/or formation. Because most current therapies are antiresorptive and resorption markers respond more quickly to these therapies, resorption markers have received the greatest attention. 

Sodium fluoride (NaF) promotes the proliferation and activity of osteoblasts and is classified as a nonhormonal bone-forming agent. Because treatment with NaF induces bone formation, it is essential that this therapy be coupled with oral calcium supplementation (1,000 mg/day). Additionally, NaF exhibits moderate antiresorptive activity, because it inhibits osteoclastic activity when it is absorbed into the bone matrix. In the treatment of osteoporosis, the therapeutic window for this agent is fairly narrow Doses less than 45 mg/day are subtherapeutic, and doses in excess of 75 mg/day impair bone mineralization. In addition, the bone that is formed in the presence of NaF is neither as well mineralized nor as strong as normal bone tissue. In fact, some... 

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