Bone Response to Resistance and Impact Exercise (BRRIE) in Women on Antiresorptive Medications: A Randomized Controlled Trial

Pharmacological and exercise interventions aimed to treat osteoporosis are typically examined separately. A common pharmacological treatment for osteoporosis involves antiresorptive medications, which has been previously shown to blunt the bone response to exercise. Many studies have shown that moderate-high intensity progressive resistance training (PRT) and impact exercise is required to stimulate bone. There are only two RCT studies that examined the effect of progressive resistance training or impact exercise on bone response in participants taking antiresorptive medications. One study showed that the combination of antiresorptive medications and resistance training did not increase bone mineral density (BMD) to a greater extent than medications alone in postmenopausal women. Another study demonstrated no additive effect of antiresorptive medications and progressive impact exercise on reducing bone turn over markers (BTMs) in postmenopausal women. However, there are currently no available studies that examine the effect of both progressive resistance training along with impact exercise on the bone response in women taking antiresorptive medications. Most exercise studies exclude people taking medications that affect bone, or are heterogeneous with respect to antiresorptive medication use. Further, there is little data on the safety of moderate-high intensity PRT and impact exercise in individuals at moderate or high risk for fracture.

The bone response to medications and exercise can be measured via the assessment of bone biomarkers present in the blood. For instance, sclerostin is a protein secreted by osteocytes and it can influence the bone remodeling process by inhibiting bone formation. Human genetic disorders deficient in sclerostin, such as sclerosteosis and Van Buchem's disease, have been associated with significant increases in bone mass. Therefore, decreasing sclerostin levels may be a potential treatment for people with low bone mass conditions. A case-control study demonstrated that postmenopausal women who adequately responded to bisphosphonates (e.g., did not experience a fracture while on treatment) had significantly lower serum sclerostin concentrations than those who experienced a fracture while taking bisphosphonates. There is also a link between sclerostin and exercise as a previous cross-sectional study reported an association between low serum sclerostin levels and increased physical activity duration. In addition, PRT and high impact exercise interventions have been shown to decrease sclerostin levels in healthy pre-menopausal women and thus may eventually increase bone mass or prevent bone loss. Therefore, changes in serum sclerostin levels can be used to provide insight regarding the bone response to antiresorptive medications as well as exercise.

Investigators plan to conduct a single-blinded parallel-group randomized controlled trial (RCT) with 1:1 allocation ratio to determine whether participants with low bone mass are able to adhere and safely perform PRT and impact exercises at an intensity that is hypothesized to stimulate bone. Specifically, the primary aim will be to determine the effects of moderate-high PRT and impact training on sclerostin in women on antiresorptive medication. The secondary aims are: a) to explore the effects of moderate-high PRT and impact training on BTMs [serum N-terminal procollagen of type I collagen (P1NP), C-terminal cross-linked of type I collagen (CTX), parathyroid hormone (PTH), Vitamin D and serum calcium], physical function and quality of life and body composition; b) to determine the feasibility of the intervention by assessing adherence, participant satisfaction with the intervention, and the acceptability of the attention control group; and c) to determine if there are any adverse events, including falls, fractures, or other adverse health outcomes attributable to the exercise intervention.

Investigators hypothesize that a moderate-to high PRT and impact exercise program will decrease sclerostin levels to a greater extent than the posture and balance exercise program. Further, it is hypothesized that PRT and impact exercise will result in more favourable improvements in other bone biomarkers, physical function, mobility, quality of life and body composition than the control group. Investigators hypothesize a low drop-out rate since both groups will be receiving the same level of attention throughout the study. Further, no adverse events attributable to exercise are expected. Kinesiologists who are Certified Exercise Physiologists will provide coaching on proper form, and will use appropriate progression of exercise intensity and volume.

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