title: The influence of antiresorptive bone medication on the effect of bone-targeted exercise on indices of fracture risk in postmenopausal women with low bone mass
Creators: name: Kistler-Fischbacher, Melanie
Publisher: name: Griffith University
Year: 2021
Subjects: subject: High-intensity resistance and impact training
subject: HiRIT
subject: Bone health
subject: Fall and fracture risk
subject: Postmenopausal women
subject: Middle-aged men
subject: Older men

description: First-line therapy for postmenopausal osteoporosis comprises antiresorptive medication such as bisphosphonates (BPs) and denosumab (Dmab; a human monoclonal antibody). Exercise is an effective non-pharmacological stimulus for bone, however, is traditionally dismissed as a singular therapy for osteoporosis. High-intensity resistance and impact training (HiRIT) applies the principles of osteogenic loading determined from animal trials. There is increasing evidence to support the feasibility and efficacy of HiRIT to safely improve bone health and indices of fall and fracture risk in postmenopausal women and middle-aged to older men. We hypothesised that the combination of exercise and bone medication may provide a more effective bone stimulus than either alone. To examine the influence of antiresorptive medication on the effects of bone-targeted exercise, we conducted a systematic review and meta-analysis of existing evidence, and a novel, randomised controlled exercise trial in postmenopausal women either on or off medication therapy. The thesis comprises five manuscripts, presented as four publications and one manuscript in preparation for submission. The first two manuscripts present a two-part review series on the effect of exercise intensity on bone in postmenopausal women. Part one is a systematic review (Chapter 3) and part two, a meta-analysis (Chapter 4). The systematic review included 100 trials, which examined the effect of 120 exercise interventions on bone mass, bone structure or bone turnover markers (BTMs) in healthy postmenopausal women on or off bone medication. Classification of each exercise intervention into low, moderate and high intensity, using predefined classification criteria, revealed the majority (95%) of trials have applied low to moderateintensity loading. Effects of exercise on bone structure and BTMs has only been evaluated in a small proportion of trials and heterogeneity of trial design and outcome measures made it difficult to draw conclusions. The meta-analysis included 53 RCTs (63 interventions) which reported BMD results derived from dual-energy X-ray absorptiometry (DXA). Results showed a positive relationship between exercise intensity and bone response for lumbar spine (LS) and total hip (TH) BMD, whereas femoral neck (FN) results were less conclusive, possibly due to the small number of studies in the high-intensity category. Resistance training was the most effective exercise type, potentially in combination with weight-bearing impact activities. Furthermore, preliminary evidence suggests that exercise (any type, any intensity) significantly reduces the risk of osteoporotic fracture. There was a small benefit of adding exercise to medication therapy at the FN but not at the LS or TH. Results are limited to a small number of studies to the extent that the influence of exercise intensity on medication therapy could not be examined. The three subsequent manuscripts comprise the study protocol (Chapter 5), and the main outcomes (Chapter 6) and secondary outcomes (Chapter 7) of the Medication and Exercise for Osteoporosis (MEDEX-OP) trial. The MEDEX-OP trial was an eight-month, randomised controlled exercise trial of postmenopausal women with low bone mass (T-score ≤ -1.0), on or off stable doses of antiresorptive bone medications (BPs or Dmab) for at least 12 months at entry. Eligible participants were randomly assigned, stratified by medication intake, to twice-weekly, 40-min, supervised HiRIT or a low-intensity control exercise intervention (Buff Bones®, BB) matched for training frequency and duration. Outcomes included spine, hip, forearm and whole body BMD, bone structure at the proximal femur, body composition, anthropometrics, indices of functional performance and posture, number of falls and fractures, quality of life related to mental and physical health and pelvic floor health, osteoarthritis symptoms, physical activity enjoyment, and willingness to pay for supervised bone-targeted exercise classes. Exercise and medication compliance and safety of the intervention (adverse events and injuries) were also monitored. A total of 115 participants were randomised at baseline; BB n = 44, HiRIT n = 42, BB-med n = 14, HiRIT-med n = 15. We found that HiRIT plus medications improved proximal femur BMD more than HiRIT-only or BB on medications. HiRIT was superior to BB for LS and trochanteric BMD, back and leg extensor strength, functional mobility and stature. We observed positive relationships between the maximum weight lifted in the deadlift exercise and changes in LS BMD and back muscles strength, as well as between maximum squat weight and changes in leg muscle strength. Compliance and retention rates were high for all groups. HiRIT increased willingness to pay for bone-targeted exercise and physical activity enjoyment, whereas BB only increased the latter. Neither of the programs led to changes in quality of life related to physical and mental health, pelvic floor dysfunction and osteoarthritis, nor resting blood pressure and heart rate. In summary, the current work confirms the benefits of HiRIT for musculoskeletal health and suggests that the combination of bone-targeted exercise with antiresorptive medication may be more beneficial for proximal femur BMD than either intervention alone. There is a positive relationship between exercise intensity and bone response at the spine and hip. The direct comparison of high to low-intensity exercise revealed superior effects of high-intensity exercise for spine, hip and forearm BMD, muscle strength and mobility and stature. We conclude that HiRIT is an efficacious, safe and appealing exercise program that is superior to other, bonetargeted exercise interventions applied at low to moderate intensity. The combination of HiRIT with first line antiresorptive medication therapy may be superior to HiRIT-alone for hip bone strength, however, a large-scale trial is needed to fully investigate this interaction.