•Gastrointestinal (GI) events and compliance with oral bisphosphonates were examined.•Among women starting oral bisphosphonates, 28% had at least 1 GI event on therapy.•GI events significantly reduced the odds of compliance with therapy by 29%.

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Fragility fractures associated with osteoporosis constitute a significant public health concern. Clinical trials have shown that a variety of agents—bisphosphonates, raloxifene, calcitonin, hormone replacement therapy, teriparatide, and strontium ranelate—can reduce the risk of osteoporosis-related fragility fractures. However, low levels of compliance and persistence in the real-life setting mean that efficacy benefits observed in clinical trials with these agents may not translate into equivalent effectiveness in daily practice. The aim of this review is to provide a comprehensive evaluation of compliance and persistence data from retrospective/observational studies, with particular reference to studies that consider the effects on fracture rates. PubMed of the National Center for Biotechnology Information (NCBI) and Web of Science databases were searched for publications detailing observational or retrospective analyses of adherence, compliance, and persistence with osteoporosis therapies. In addition, authors provided relevant studies that were not retrieved using the search criteria. In total, 17 unique publications were identified. Analysis of the publications indicated that low compliance and persistence rates for osteoporosis therapies in the real-life setting result in increased rates of fragility fractures. The results emphasize the importance of good treatment compliance and persistence with osteoporosis therapies in order to achieve a significant therapeutic benefit and thereby reduce the burden that osteoporosis and associated fractures place on individuals and healthcare systems.

We have read with interest the paper by Siris et al. from the NORA Study. We agree with the data presented, and it agrees with studies previously published by ourselves and others. However, the title “Predictive Value of Low BMD for 1-Year Fracture Outcomes Is Similar for Postmenopausal Women Ages 50–64 and 65 and Older” is misleading, as is the last sentence of the abstract “we found the relationship of BMD measured at peripheral sites and subsequent 1-year fracture risk to be similar between women <65 and those 65 years of age.” The conclusion after the introduction, “low BMD in younger postmenopausal women 50-64 years of age showed a 1-year relative risk of fracture similar to that found in women >65 years of age” is correct. The relative risk for fracture remains the same or is lower with increasing age. However, the absolute risk of fracture—that which is most important in clinical decision-making—increases with age. Thus, the same relative risk at an older age translates into a large excess risk of fracture. From the graph of all fractures in Fig. 1, we can see that, among women 50–64 years of age, those with T scores −2.0 have an excess risk of about 14 (based on 20 − 6) fractures per 1000 person-years compared with women with T scores > 1.0. In contrast, among women 65 years of age, women with T scores 2.0 have an excess risk of about 20 (based on 29 − 9) fractures per 1000 person-years. From the same figure, the same difference in T scores would confer an excess of about one hip fracture per 1000 person-years in the younger women and about six hip fractures per 1000 person-years in the older women. Thus, a T score of −2.0 at age 75 carries with it a greater excess in absolute risk of fracture over the next few years than a similar T score at age 55 compared with women with a T score of 0 at their respective ages. The distribution of fractures also is different, with the incidence of the more severe hip fracture being 0.8 per 1000 patient-years in younger women and 3.9 per 100 patient-years in older women. It is important that this concept be familiar to practitioners making decisions based on T scores. This is perhaps a strong reason to move on to a system based on absolute risk.

The relationship of low bone mass and fracture in younger postmenopausal women has not been extensively studied. In a large cohort of postmenopausal women :50 years of age, we found the relationship of BMD measured at peripheral sites and subsequent 1-year fracture risk to be similar between women <65 and those >= 65 years of age.Introduction: Low bone mass and fractures are prevalent in older postmenopausal women. However, the frequency of low bone mass and fracture in younger postmenopausal women has not been studied extensively. There are very limited data regarding the association between BMD measurements and fractures in postmenopausal women who are between the ages of 50 and 64.Materials and Methods: In the National Osteoporosis Risk Assessment (NORA) we studied the frequency of low bone mass and its association with fracture in women 50-64 years of age in comparison with women >= 65 of age. NORA enrolled 200,160 postmenopausal women >= 50 years of age who had no prior diagnosis of osteoporosis. Baseline BMD was measured at the heel, forearm, or finger. A 1-year follow-up survey requesting incident fractures since baseline was completed by 163,935 women, 87,594 (53%) of whom were 50-64 years of age. The association between BMD and fracture was assessed using logistic regression, adjusted for important covariates.Results: Thirty-one percent of women 50 - 64 years of age had low bone mass (T scores <= - 1.0) compared to 62% of women >= 65 years of age. During the first year of follow-up, 2440 women reported fractures of wrist/foreann, rib, spine, or hip, including 440 hip fractures. Nine hundred four women 50-64 years of age reported fractures, including 86 hip fractures, accounting for 37% of fractures and 20% of hip fractures reported in the entire NORA cohort. Relative risk for osteoporotic fracture was 1.5 for each SD decrease in BMD for both the younger and older groups of women.Conclusion: Low BMD in younger postmenopausal women 50-64 years of age showed a 1-year relative risk of fracture similar to that found in women >= 65 years of age.

Drug therapy isn't recommended for all women with osteopenia, a precursor to osteoporosis. Clinicians need to identify, early on, the patients with low bone mass at additional risk for future osteoporotic fractures.

Selective estrogen receptor modulators (SERMs) have been introduced into clinical practice for the treatment of breast cancer (tamoxifen, toremifene), the reduction in risk of breast cancer in high-risk women (tamoxifen) and the prevention and treatment of osteoporosis in postmenopausal women (raloxifene). These diverse clinical activities are tied together by virtue of the mechanisms of action of these compounds, which center on their interaction with estrogen receptors. This chapter reviews recent advances in understanding these mechanisms, followed by a review of data that supports the clinical use of SERMs. The number of potential mechanisms that may explain the tissue-selective actions of SERMs is growing steadily as new findings are uncovered. Central to all of these mechanisms are the differential effects that SERMs exert on the three-dimensional conformation of the ligand-bound receptor. The specifics of the roles of the various domains of the receptor are beginning to unfold. In particular, the molecular mechanisms underlying the function of the AF-2 region have become increasingly clear with publication of X-ray crystallographic depictions of the receptor bound to various ligands and peptide fragments of co-activator proteins. Emerging understanding of the tissue distribution and functional biology of the estrogen receptor isoforms has filled in even more of the complex picture. These evolving insights should provide the platform for an even better understanding of estrogen and SERM action while providing the basis for continued rational drug discovery. From the clinical perspective, the ideal SERM would offer the postmenopausal woman all the benefits of estrogen replacement without the potential estrogen-mediated adverse effects: it would relieve menopausal symptoms, including vaginal dryness and hot flashes.

OBJECTIVE:To characterize the historical, clinical, and biochemical features of 111 young women (age, <55 years) referred for evaluation of osteoporosis or low bone mass.METHODS:Women with a bone mineral density T score < or = -2.0 (N = 111) at one or more anatomic sites (by dual-energy x-ray absorptiometry) were assessed relative to anthropomorphic and biochemical characteristics and risk factors for osteoporosis.RESULTS:Of 111 women with low bone mass or osteoporosis, 73 (66%) had identifiable causes of bone loss, of which estrogen deficiency (menopause, premenopausal estrogen deficiency) and conditions associated with estrogen deficiency (anorexia nervosa, cancer chemotherapy) were the most common. Prolonged use of glucocorticoids was the most common secondary cause of osteoporosis. Of 38 women with no identifiable cause of bone loss, 21 were premenopausal (mean age, 38 +/- 10 years [standard deviation]) and 17 were perimenopausal (mean age, 50 +/- 3 years). The mean lumbar spine T score was -2.18 +/- 1.0 in the premenopausal and -2.51 +/- 0.6 in the perimenopausal women. Nontraumatic fractures were reported by 42% of the premenopausal women and 18% of the perimenopausal women. A family history of osteoporosis was reported by 71% of the premenopausal and 47% of the perimenopausal women.CONCLUSION:Most young women with osteoporosis or low bone mass had estrogen deficiency or another secondary cause of premature bone loss (or both). A subset of premenopausal and perimenopausal women, however, had no identifiable cause of bone loss. The strong family history of osteoporosis, especially in the premenopausal women, provides further support for current theories of a genetic predisposition to osteoporosis.