New research and recommendations were presented at ASBMR 2019, the American Society for Bone and Mineral Research annual meeting, from September 20-23 in Orlando. The features below highlight key presentations from the conference.
High-Dose Combination Therapy Further Increases BMD
Prior research indicates that co-administration of denosumab and teriparatide can result in greater and faster increases in spine and hip bone mineral density (BMD) than could be achieved with either alone or with any other drugs on the market. To determine if even larger and more rapid gains in bone mass could be achieved by combining denosumab with a larger anabolic stimulus, researchers randomized postmenopausal women at high fracture risk to high- or standard-dose teriparatide for 9 months; all women received denosumab every 6 months during months 3 to 15. At 15 months, spine and total hip BMDs increased 17.5% and 6.1%, respectively, in the high-dose group, compared with 9.5% and 3.9%, respectively, in the standard-dose group. Bone density at the femoral neck at 15 months increased 6.8% in the high-dose group, compared with 4.3% in the standard-dose group; respective trabecular spine density increases were 32% and 13%.
Calcium Supplementation & CV Health at 1 Year
Whether calcium supplementation increases the risk for cardiovascular (CV) events in older women has been debated in recent years, with studies providing unclear results. Using carotid femoral pulse wave velocity (cfPWV) as an indicator of arterial stiffness and carotid intima-media thickness (cIMT) as an indicator of subclinical atherosclerosis, researchers sought to determine whether calcium supplementation resulted in pre-symptomatic markers for CV disease. Women in the study randomized to a daily 750-mg supplement plus 450 mg via diet displayed no differences in measures of either indicator at 12 months when compared with those assigned to 450 mg of calcium through diet alone and a control group assigned to no intervention. No significant differences were observed between the groups in serum total cholesterol or high-sensitivity c-reactive proteins either. However, the study only included 121 participants and had a follow-up of only 1 year, not allowing enough time to truly assess for CV events like myocardial infarction or gradual structural changes in vessels.
Lean Mass Loss Predicts Fracture Risk
The widely used fracture risk assessment (FRAX) tool considers BMI measurements derived from height and weight as baseline measures, but the tool does not assess either component over time. To assess the longitudinal effects of two components of weight loss, study investigators used an estimated body composition measure based on weight, sex, and percent fat measured from the abdomen and hip dual energy x-ray absorptiometry (DEXA) in nearly 10,000 patients aged 40 and older who had two spin-hip assessments in the DEXA Registry and Repository at least a year apart. Reductions in total body lean mass were associated with a significantly higher risk for fracture, with every standard deviation in lean mass loss associated with a 10% to 13% increased risk for major osteoporosis fractures, even after adjustments for height loss, FRAX scores with and without bone density, and competing mortality. Each standard deviation in lean mass loss was also associated with a 29% to 38% increase risk for hip fracture. Total body fat mass loss was not associated with significantly increased risks for either.
Atypical Femoral Fracture Risk Increased in Asian Women
Data indicate that, in general, Asian people have more curved femurs when compared with other ancestries. To compare the risk for atypical femoral fracture (AFF), almost 200,000 women older than 50 who had at least one dispensed bisphosphonate prescription were prospectively enrolled in a study. When compared with Caucasian ancestry, Asian ancestry was associated with a nearly five-times greater risk for AFF, with no significant differences seen between ethnic subgroups. Risk remained similar between Asian and Caucasian women after accounting for height, weight, and prior fracture. Risk also remained similar regardless of bisphosphonate treatment duration as well as for the number of years participants had been off osteoporosis treatment, with time since last medication associated with improved risk for all women.
Bone Loss Mediated With Probiotics
Prior research suggests that gut microbiota can help shape the immune system, with other studies indicating that the immune system can regulate bone mass. Animal studies have also shown that the gut microbiota can regulate bone mass, with small human studies suggesting limited effects of probiotics in older women. To determine if such findings would remain in better-powered research, investigators conducted a multicenter, placebo-controlled trial of women in early menopause for whom active treatment consisted of daily capsules containing Lactobacillus paracasei DSM 13434, L. plantarum DSM 15312, and L. plantarum DSM 15313. While women randomized to placebo developed significant lumbar spine BMD loss after 1 year (-0.77%), those on probiotic therapy developed no significant loss (-0.17%). Women who were less than 6 years postmenopausal experienced the greatest protective effect, with lumbar spine BMD loss of -0.18% for the probiotic group and -1.21% for the placebo group. Adverse events were similar between the groups.