Cases in Menopause
Conjugated estrogen plus bazedoxifene—a new approach to estrogen therapy
For which of my patients is this treatment appropriate?
Deficiency of this vitamin causes growth retardation and rickets in children and osteomalacia in adults and can precipitate and exacerbate osteopenia or osteoporosis and increase the risk of fracture in adults.
Some evidence also suggests that vitamin D deficiency may have other serious consequences, including an increased risk for common cancers and autoimmune, infectious, and cardiovascular diseases.
In this review, Holick argues that we need to remind our patients of the beneficial effects of moderate sunlight.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
There is no question that sufficient levels of vitamin D are vital to bone health, and perhaps to overall health in numerous other organ systems as well. The pendulum of our concern over skin cancers may have moved too far in the direction of sun avoidance. In reality, moderate sunlight as a source of vitamin D is still appropriate for many of our patients.
WHEN IT COMES TO ESTROGEN AND BONE, BENEFITS OUTWEIGH RISKS
de Villiers TJ. 8th Pieter van Keep Memorial Lecture. Estrogen and bone: have we completed a full circle? [published online ahead of print September 22, 2014]. Climacteric. 2014;17(suppl 2):4–7. doi:10.3109/13697137.2014.953047.
In the WHI estrogen-progestin arm, fracture rates were reported as hazard ratios:
- hip fracture, 0.66 (95% confidence interval [CI], 0.45–0.98)
- clinical vertebral fracture, 0.66 (95% CI, 0.44–0.98)
- nonvertebral fractures, 0.77 (95% CI, 0.69–0.86).
In the estrogen-only arm of the WHI, reductions in the rates of fracture were reported as percentages and were similar:
- 39% reduction in hip fracture, compared with placebo
- 38% reduction in clinical vertebral fracture
- 21% reduction in total fractures.
All of these reductions were statistically significant.
Despite the excellent anti-fracture efficacy demonstrated in the WHI, investigators concluded that the risks of hormone therapy outweighed the benefits in the general postmenopausal population.
Why we should reconsider estrogen for bone health
In his presidential address to the International Menopause Society (cited above), de Villiers observed that, in the WHI:
- Only clinical fractures were recorded. Unlike all other fracture trials, routine radiographs were not obtained to record morphometric fractures. This decision, he believes (and I concur), led to a significant understatement of estrogen’s protective effects against vertebral fracture.
- The general population studied had a low risk of fracture, with an average spinal T-score of –1.3. This, too, contributed to an understatement of estrogen’s protective effects, compared with the findings of other randomized controlled trials involving patients at much higher risk.
- From a bone-centric point of view, the WHI findings represent a favorable ratio of benefits to risks.
No bone-active drugs are completely free of potential adverse effects and restrictions, many of which become apparent only after FDA approval and general use of the drug. Bisphosphonates have been implicated in atrial fibrillation, osteonecrosis of the jaw, and atypical femur shaft fracture after extended use. Like estrogen, SERMs can increase the risk of death from deep venous thrombosis and stroke.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Estrogen is the only agent proved to be effective against all types of osteoporotic fractures during primary analysis of a large randomized controlled trial. This efficacy is of special importance for the patient with osteopenia who is at risk for fracture. Estrogen remains a serious option for the prevention of postmenopausal bone loss and osteoporosis-related fractures, especially in younger patients. Individualization of therapy is key.
COUNSEL SSRI AND SNRI USERS THAT BMD MAY DECLINE OVER THE LONG TERM
Ak E, Bulut SD, Bulut S, et al. Evaluation of the effect of selective serotonin reuptake inhibitors on bone mineral density: an observational cross-sectional study [published online ahead of print September 4, 2014]. Osteoporos Int. doi:10.10007/s00198-014-2859-2.
Moura C, Bernatsky S, Ambrahamowicz M, et al. Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS). Osteoporos Int. 2014;25(5):1473–1481.
Bruyère O, Reginster J-V. Osteoporosis in patients taking selective serotonin reuptake inhibitors: a focus on fracture outcome [published online ahead of print August 5, 2014]. Endocrine. doi:10.1007/s12020-014-0357-0.
Evidence from longitudinal, cross-sectional, and prospective cohort studies suggests that the use of antidepressants at therapeutic doses is associated with a reduction in BMD and an increase in the risk of falls and fracture. These associations have been demonstrated in several distinct populations using various study designs, and with bone density, bone loss, or fractures as outcomes. They remain consistent even after adjustment for confounding variables such as age, body mass index, lifestyle factors such as alcohol and tobacco use, and fracture history.
Ak and colleagues recruited 60 patients given a diagnosis of generalized anxiety disorder and treated with paroxetine, sertraline, or citalopram for at least 12 months, comparing their BMD with that of 40 healthy volunteers. BMD was measured by dual-energy x-ray absorptiometry at the femoral and lumbar regions. BMD of the L2–L4 vertebrae, total lumbar vertebrae, and femoral intertrochanteric region, as well as total femoral Z-scores and femoral Ward’s region T-scores, were lower in the treatment group (P<.05). There was a significant negative correlation between the duration of treatment and the change in BMD values.
