A two-year, controlled, double-blind bridging study has been performed in osteoporotic men. The objective was to study men with a similar risk profile as the postmenopausal women previously included in the pivotal phase 3 trials, therefore the BMD inclusion criterion was below a same absolute BMD threshold value as in the studies in women. In a preliminary communication of the results
at one year (main study analysis), the authors reported that a same dosage of strontium ranelate with calcium and vitamin D supplementation resulted in similar strontium blood levels and a similar significant BMD gain at the spine and hip in osteoporotic men compared with osteoporotic postmenopausal women [97]. Of note, an open-label, prospective, controlled, BMD endpoint 12-month trial in male osteoporosis patients compared strontium ranelate 2 g/day (n = 76) vs. SB431542 supplier alendronate 70 mg/week, an agent already approved for male osteoporosis. Mean increases selleck kinase inhibitor in lumbar spine and total hip BMD were greater with strontium ranelate compared with alendronate [98], although the increment in BMD is partly dependent on a treatment-induced artefact. These strontium ranelate data support the increases in BMD observed in the recent core bridging study. Odanacatib inhibits cathepsin-K,
a protease that plays an important part in osteoclast function. A phase III odanacatib trial in men with osteoporosis is ongoing (NCT01120600). In postmenopausal women, the effect of odanacatib on biochemical markers of bone turnover (sCTX, bALP) and on
change in lumbar spine and femoral neck BMD (vs. baseline) was promising at 24 and 36 months [99] and [100]. Femoral neck BMD decreased after odanacatib discontinuation, although it remained above baseline levels [100]. Therapies currently in phase II development include sclerostin inhibitors [101]. Data obtained in sclerostin knock-out (KO) mice have shown that these have high bone mass and normal bone morphology, but with increased trabecular and cortical bone volume. Other than the bone phenotype, no additional biologically significant differences were observed between wild-type and KO mice. Based on micro CT imaging, female KO mice appeared to have increased bone volume compared with males [102]. Anti-sclerostin antibody was also shown to increase markers of bone formation and BMD in healthy men and postmenopausal women 4��8C [103]. The stimulation of spontaneous endogenous PTH secretion, using calcium receptor agonists that tend to reduce serum calcium (calcilytics), has been proposed as an alternative approach to teriparatide administration. Examples of such compounds include ronalcaleret and JTT-305. Ronalcaleret had no effect on BMD, possibly because of a prolonged stimulation of PTH secretion [104]. JTT-305 was tested over three months in 154 postmenopausal osteoporotic women randomised to three groups: placebo (n = 51), 10 mg/day (n = 50) and 20 mg/day (n = 53).