Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

Assessment and hormonal management of osteoporosis.

Postmenopausal osteoporosis is a frequent health issue in women. Because osteoporosis-related fractures cause a significant increase in mortality and morbidity, it is clinically important to identify as soon as possible women at increased risk for future fracture so that preventive measures can be instituted. At the beginning of menopause, evaluation of the subsequent risk of fracture is not so easy. Most screening tools fail to accurately identify those women who will fracture within the next 10 years. A history of a prior fracture and low bone mineral density are the only major consistently found predictors for the risk of fracture. On the other hand, it is no longer a question whether menopause hormone therapy is efficient not only to prevent postmenopausal bone loss but also the incidence of fragility fracture. Over the last years, utility of menopause hormone therapy for the prevention of osteoporosis has been questioned due to safety concerns. In light of the most recent reports on a more favorable benefit/risk balance than was initially claimed in early postmenopausal women, this needs to be reconsidered. Prevention of bone loss in those women with a moderate or slightly high risk of fracture is likely a strategy to reduce fracture risk in older women. Menopause hormone therapy must be considered as a true primary preventive therapy more than an anti-fracture therapy at an age when the risk of fracture is likely much lower than later in life. Only thereafter should other anti-osteoporotic medications be discussed in women still at high risk for fracture.

[What patients need to know about the risk of bone fracture and its prevention]. / Ce que les patientes doivent savoir sur le risque osseux et sa prévention.

Post-menopausal osteoporosis is one of the classic complications of prolonged estrogen deficiency associated with menopause. It is defined as a state of the skeleton characterized by decreased bone strength with an increased risk of fracture. The natural history of osteoporosis and, in particular, the rapid increase in fracture recurrence after a first major fracture should justify a priori an approach for early detection of women at higher risk from the early postmenopausal phase. It is more of a chronic disease that requires support in the long term, in the absence of a truly curative treatment. Indeed, currently available therapies can at best reduce the incidence of fractures by about 50%, especially at the vertebral site, but do not cancel the disease. Moreover, duration of treatment is currently recommended for 5 to 10 years, which does not allow to consider that a single molecule could be taken "for the whole life". The fracture risk assessment based on the combination of densitometric measurement by DXA and the search for clinical risk factors is a prerequisite to any therapy. The first choice of treatment is especially important for a relatively young woman with high fracture risk. In early menopause (generally within the first decade of post-menopausal) and in the absence of contraindication, menopausal hormone therapy should remain the preferred option for first-line whenever possible. Raloxifene is an interesting alternative, due to its mechanisms of action and multiplicity of targets with, in particular, its preventive effect on the risk of estrogen receptor-positive breast cancer. It is only when there are contraindications to one or the other of these two molecules, that other osteoporosis treatments can be discussed. They should nevertheless be considered only in women whose 10-year-fracture risk is significantly increased. Indeed, it is mainly in this high risk of fracture, particularly because of an age greater than 65 years and a history of vertebral fracture, that their antifracture efficacy has been validated. In addition, it is mostly beyond this age that the question of the prevention of hip fracture has to be considered.

[How to prevent early postmenopausal fracture risk? Proposition of a strategy]. / Proposition d'une stratégie de prévention du risque fracturaire en début de ménopause.

Postmenopausal osteoporosis is a chronic disease, which justifies long-term treatment in those women with an increased risk of fracture. The current disponibility of various drugs, which have demonstrated their efficacy in reducing the incidence of fracture, has raised the question of the best treatment strategy in a woman who would begin her postmenopausal period with an increased risk for fracture. Indeed, for most treatments (with the exception of hormonal replacement therapy [HRT]), their efficacy in reducing the risk of fracture has been mainly demonstrated in higher risk elderly women (above 65 years) with prevalent vertebral fractures. There is uncertainty concerning their cost-effectiveness in younger women for a true primary prevention of the risk of fracture. Furthermore, current guidelines recommend a 5-year period of treatment which has led us to considering treatment strategies which would be based on various sequential treatment periods over time, the selection of each specific sequence being determined by the clinical situation of the woman, the level of her fracture risk and the expected skeletal (in terms of spectrum of bone effects) and potential extraskeletal benefits of drugs. In this regard, HRT or raloxifene, which allows a more global approach of the menopause-induced consequences of estrogen deficiency than the sole prevention of osteoporosis, should be privileged within the first 10 years of treatment or so in those youngest women at increased risk for subsequent fracture. Use of bisphosphonate or strontium ranelate should be thus reserved at a more advanced age, when the prevention of hip fracture becomes mandatory.

Spine and femur densitometry at the menopause: are both sites necessary in the assessment of the risk of osteoporosis?

The aim of our study was to compare the results provided by the measurement of vertebral and femoral bone mineral density (BMD) for assessing the individual risk of osteoporosis as defined by either low BMD and/or rapid bone loss. Vertebral and femoral BMD were measured twice at a mean interval of 21 months in 85 normal, early postmenopausal women who had passed a natural menopause 6 months to 3 years previously. According to the measurement site, 36% (spine), 29% (femoral neck), 35% (Ward's triangle), and 25% (trochanter) fall in the "at risk" category, defined by a BMD value of 1 SD or more below the normal values for premenopausal women. Based on vertebral BMD, 39-48% of the women at risk had a normal femoral BMD. On the other hand, 24-37% of the women classified at risk based on femoral BMD maintained a low risk at the vertebral level. The annual rate of bone loss was significantly greater for the Ward's triangle (-2.7 +/- 3.8%) and femoral neck (-2.1 +/- 2.5%) than for the spine (-1.5 +/- 2.1%) and trochanter (-1.5 +/- 3.4%). There was a significant relationship between the rate of loss measured at the spine and femoral levels (r = 0.34-0.58). Among the 21 women with a rapid vertebral bone loss, 48-67% had a low bone loss at the femoral level and vice versa. The ratio between mean rate of loss and the precision of the measurement sites was greater for the spine (1.6) compared with the femur (1.1-0.71).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of the risk of post-menopausal osteoporosis using clinical factors.

OBJECTIVE: We wished to assess the predictive value of the main clinical risk factors for osteoporosis over a low vertebral bone mineral density. DESIGN: A cross-sectional study was made of a cohort of peri and post-menopausal women (mean age, 54 years). PATIENTS: One thousand, five hundred and sixty-five normal white women were selected from among the women referred to our menopause clinic for screening and prevention of osteoporosis. MEASUREMENTS: Each woman had replied to a detailed standardized questionnaire including the main clinical risk factors and had her bone density measured using dual photon absorptiometry. RESULTS: The predictive value for a low vertebral bone mineral density (2 SD below the normal young adult value) was assessed for 15 historical and anthropometric variables. Among these, age, age at menarche, weight, height, menopause and its duration, were independent predictors of a low bone mineral density, in a multiple logistic regression analysis. Odds ratios were calculated for each of these variables, weight, menopause and its duration being the three most influential variables. At best this model makes it possible to correctly classify 73% of women with a low bone mineral density and 66% of those with a normal bone mineral density. If this model is used for screening, it could possibly save 25% of bone densitometry examinations. CONCLUSIONS: Direct bone densitometry remains indispensable to assess osteoporosis risk, since risk factors alone are not sufficient for accurate delineation of either low or normal bone mineral density.