Cases in Menopause
Conjugated estrogen plus bazedoxifene—a new approach to estrogen therapy
For which of my patients is this treatment appropriate?
Moura and colleagues reviewed data from a large prospective Canadian cohort to assess the association between SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), and fracture in adults aged 50 and older. They used the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based community cohort.
Among 6,645 subjects, 192 (2.9%) were using SSRIs or SNRIs, or both, at baseline. During the 10-year study period, 978 participants (14.7%) experienced at least one fragility fracture. SSRI/SNRI use was associated with an increased risk of fragility fracture (hazard ratio [HR], 1.88; 95% CI, 1.48–2.39). After controlling for multiple risk factors, previous falls, and BMD of the hip and lumbar bone, the adjusted hazard ratio for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32–2.14). The authors concluded that these results lend additional support to an association between SSRI/SNRI use and fragility fractures.
A few possible underlying mechanisms support the biological plausibility of these observations. One explanation is that increased fracture risk is mediated simply by falling. Another explanation could involve the influence of serotonin on bone. Besides their effects on balance, SSRIs may influence bone turnover and BMD. Whatever the mechanism, sufficient evidence exists to warrant the addition of SSRIs to the list of medications that contribute to osteoporosis.
Antidepressant use is not listed as a secondary cause of osteoporosis in the FRAX algorithm. Because the association between SSRI use and fracture risk appears to be independent of BMD, it may be useful to consider the possibility of including it in FRAX.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Consider BMD assessment for patients who take an SSRI, or who take an SSRI and have additional risk factors for fracture. Given the body of data on this issue, it seems appropriate to expect providers of SSRIs to conduct at least some discussion of bone health with patients.
IN THE PIPELINE: A HIGHLY EFFECTIVE AGENT TARGETING SCLEROSTIN
Recker R, Benson C, Matsumoto T, et al. A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density [published online ahead of print September 5, 2014]. J Bone Miner Res. doi:10.1002/jbmr.2351.
Sclerostin is a protein secreted by osteocytes that negatively regulates the formation of mineralized bone matrix and bone mass. Recker and colleagues conducted a randomized, double-blind, placebo-
controlled, multicenter, phase 2 clinical trial of blosozumab, a humanized monoclonal antibody targeted against sclerostin. The year-long trial involved 120 postmenopausal women with low BMD (lumbar spine T-score, –2.0 to –3.5) who were randomly allocated to:
- subcutaneous blosozumab 180 mg every 4 weeks
- subcutaneous blosozumab 180 mg every 2 weeks
- subcutaneous blosozumab 270 mg every 2 weeks
- placebo.
All groups also received calcium and vitamin D and underwent serial measurement of spine and hip BMD and testing of biochemical markers of bone turnover. The mean age was 65.8 years, and the mean lumbar spine T-score was –2.8.
Women treated with blosozumab experienced statistically significant, dose-related increases in spine, femoral neck, and total hip BMD, compared with placebo. In the highest dose group, BMD increased 17.7% from baseline at the spine and 6.2% at the total hip. Biochemical markers of bone formation increased rapidly during treatment with blosozumab, trending toward pretreatment levels by the study’s end. CTX, a biochemical marker of bone resorption, decreased early during blosozumab treatment to a concentration lower than that in the placebo group by 2 weeks, and it remained low throughout treatment.
Mild injection-site reactions were reported more frequently with blosozumab than with placebo.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although blosozumab is not yet available, clinicians should be aware of the potential of sclerostin-antibody therapies like it. Such therapies appear to have substantial anabolic effects on the skeleton and may become promising agents in the treatment of osteoporosis.
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