Drug treatment has traditionally been considered the gold standard therapy for osteoporosis, due to limited efficacy of lifestyle interventions such as low to moderate intensity exercise and dietary interventions. Recently, however, the LIFTMOR (Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation) trial demonstrated that a novel, high-intensity progressive resistance and impact training (HiRIT) program markedly improved bone and functional indices of falls and fracture in postmenopausal women with low to very low bone mass. While men also suffer from osteoporosis, prevalence is lower than in women, leading to fewer studies in men. To determine if the same exercise protocol would be effective for older men with low bone mass, the LIFTMOR-M (LIFTMOR for Men) trial was conceived. Another recent development in the field of osteoporosis was the bioDensity™ exercise machine, designed theoretically to load bone via isometric axial compression (IAC). Although the manufacturers claimed osteogenic efficacy, no high-quality evidence existed. By examining the effects of two novel exercise programs on musculoskeletal health and risk factors for falls in a poorly researched population, our findings will contribute evidence towards developing efficacious non-pharmacological osteoporosis therapy. The current Thesis reports the results of the eight-month LIFTMOR-M exercise intervention trial. That is, we compared the efficacy, compliance and safety of supervised HiRIT in comparison to supervised machine-based IAC exercise or control (usual activities) on indices of bone strength and risk factors related to falls and fracture susceptibility in middle-aged and older men with low areal bone mineral density (aBMD).

The Thesis comprises four publications, presented as one published manuscript, one manuscript accepted for publication and two manuscripts under review. The published manuscript (Chapter 3) is the protocol paper outlining the study design, recruitment, exercise interventions, control activities, and primary and secondary outcomes of LIFTMOR-M. The trial was a three-arm, eight-month, semi-randomised controlled exercise intervention trial. Community-dwelling, middle-aged and older men (≥ 45 years) with low aBMD at the lumbar spine (LS), total hip and/or femoral neck (FN) (Tscore ≤ - 1.0) were recruited. Eligible participants were randomly assigned to eight months of twice-weekly, supervised HiRIT (five sets of five repetitions, ≥ 80-85% of one repetition maximum) or machine-based IAC exercise (five-second isometric contraction, rating of perceived exertion ≥ 16) stratified on presence or absence of osteoporosis medications. The self-selected, non-randomised control group, who received no intervention, were instructed to maintain customary dietary and physical activity patterns. Participants underwent testing at baseline and eight months. Outcomes included:​ whole body and regional bone, muscle and fat;​ anthropometry;​ indices of functional performance;​ thoracic kyphosis;​ and vertebral fracture assessment. Compliance and adverse events (falls, fractures, and injuries) were monitored. In the second manuscript (Chapter 4), we reported the primary outcome (FN aBMD) and secondary outcomes of regional aBMD, calcaneal ultrasound parameters, anthropometrics, body composition, physical performance, compliance, and adverse events. We found that HiRIT improved LS aBMD, trochanteric aBMD, broadband ultrasound attenuation and stiffness index of the calcaneus, lean mass, and five physical performance measures compared to loss or minimal change for control. IAC improved lean mass and one physical performance measure compared with control. HiRIT effects were superior to IAC for LS aBMD, stiffness index of the calcaneus and five-times sit-to-stand performance. Compliance and retention were high, and there were few adverse events. In the subsequent manuscript (Chapter 5), secondary outcomes of bone strength indices at the proximal femur, tibia and radius are presented. We found that HiRIT provided a positive stimulus to cortical bone at the medial FN compared with IAC and control, and both HiRIT and IAC preserved bone strength at the distal tibia and distal radius in comparison to control. The final manuscript (Chapter 6) presents clinical measures of thoracic kyphosis with inclinometry, Cobb angle of kyphosis and vertebral fracture assessment for a sub-group of LIFTMOR-M exercise intervention participants. We observed that both HiRIT and IAC improved clinical measures of thoracic kyphosis, and HiRIT improved Cobb angle of kyphosis, at eight months. HiRIT had no incident fractures nor progression of prevalent vertebral fractures over the course of the trial. By contrast, IAC experienced five incident vertebral wedge fractures and one wedge fracture progressed.

In summary, the current Thesis reports the positive effects of twice-weekly, supervised HiRIT on bone, muscle, kyphosis, incident vertebral fracture, and functional indices of falls and fracture risk in older men with osteopenia and osteoporosis. Furthermore, strong compliance and retention suggests HiRIT training was appealing and well tolerated, with no incident fractures or major adverse events across the intervention period. IAC may improve lean mass and posture to a lesser extent but does not improve or preserve bone at clinically relevant sites, nor prevent incident vertebral fracture. Based on these findings, we conclude that HiRIT is a safe, efficacious and appealing exercise program, superior to IAC, for the management and rehabilitation of osteopenia and osteoporosis in middle-aged and older men.