It has been hypothesized that this could be due to prolonged suppression of bone turnover, leading to accumulation of microdamage and development of hypermineralized bone, but this remains to be confirmed. Two recent histologic studies did
not show indeed an increased prevalence of microcracks in patients who had received alendronate www.selleckchem.com/products/BafilomycinA1.html for more than 5 years [103, 104], though it appears in the study by Stepan et al. that cracks become significantly more prevalent in the alendronate-treated patients with the lowest bone mineral densities. A recently published epidemiological study also suggests that these fractures are more linked to selleck compound osteoporosis itself than to bisphosphonate treatment : this registered-based cohort study has shown that the distribution of these atypical fractures was identical in an alendronate-treated cohort and in an untreated cohort, and that in a small number of patients who remained on alendronate for more than 6 years, there selleck products was no shift from typical to atypical femur fractures, which is reassuring. Further investigation is mandatory to precise the usefulness of stopping bisphosphonate (after 5 or 10 years of treatment?) or monitoring bone markers to avoid oversuppression of bone turnover. Anabolic agents The pharmacologic armamentarium available to clinicians to reduce fracture risk in women with postmenopausal
osteoporosis consists essentially of antiresorptive agents, i.e., drugs acting through inhibition of osteoclastic bone resorption and lowering of global bone turnover. The only exceptions are peptides from the PTH family, which, under specific modalities of administration, act as anabolic agents stimulating bone formation, and
strontium ranelate, which acts as an Alanine-glyoxylate transaminase uncoupling agent effecting a stimulation of bone formation with reduction of bone resorption. The interest generated by these alternatives to antiresorptive treatment resides in their greater potential for restoration of bone mass and possibly also bone structure in osteoporotic subjects who have already suffered substantial skeletal deterioration. Peptides of the PTH family have been investigated in the management of osteoporosis since more than 30 years . Their proposed use in the treatment of osteoporosis is based on the observation that intermittent exposure to low dose PTH is anabolic to the bone, in contrast to the catabolic effects on cortical bone resulting from continuous exposure to supraphysiological levels of PTH from either endogenous or exogenous origin. The anabolic effects of PTH are exerted through stimulation on the cells of osteoblastic lineage of the PTH-1 receptor, which is shared by both PTH and PTH-related peptide (PTHrP) and is therefore also known as the PTH–PTHrP receptor.