The goal of the MEDEX-OP trial was to compare the efficacy of a known effective high-intensity resistance and impact training (HiRIT) with a low-intensity exercise control (Buff Bones ® [BB]), alone or in combination with antiresorptive bone medication, on indices of fracture risk (bone mass, body composition, muscle strength, functional performance), compliance, and safety. Primary study outcomes were 8-month change in lumbar spine (LS) and total hip (TH) bone mineral density (BMD). Healthy postmenopausal women with low bone mass (T-score ≤ À1.0) on or off stable doses (≥12 months) of antiresorptive medication were recruited. A total of 115 women (aged 63.6 AE 0.7 years; body mass index [BMI] 25.5 kg/m 2 ; femoral neck [FN] T-score À1.8 AE 0.1) were randomly allocated to 8-month, twice-weekly, 40-minute HiRIT (5 sets of 5 repetitions, >80% to 85% 1 repetition maximum) or BB (low-intensity, Pilates-based training), stratified by medication intake, resulting in four groups: HiRIT (n = 42), BB (n = 44), HiRIT-med (n = 15), BBmed (n = 14). HiRIT improved LS BMD (1.9 AE 0.3% versus 0.1 AE 0.4%, p < 0.001) and stature (0.2 AE 0.1 cm versus À0.0 AE 0.1 cm, p = 0.004) more than BB. Both programs improved functional performance, but HiRIT effects were larger for leg and back muscle strength and the five times sit-to-stand test (p < 0.05). There was a positive relationship between maximum weight lifted and changes in LS BMD and muscle strength in the HiRIT groups. Exploratory analyses suggest antiresorptive medication may enhance exercise efficacy at the proximal femur and lumbar spine. Exercise compliance was good (82.4 AE 1.3%) and both programs were well tolerated (7 adverse events: HiRIT 4; BB 3). HiRIT improved indices of fracture risk significantly more than Buff Bones ® . More trials combining bone medication and bone-targeted exercise are needed.

To compare the effects of high-intensity resistance and impact training (HiRIT) to low-intensity, Pilates-based exercise (LiPBE) on proximal femur geometry and explore the influence of antiresorptive medication on those effects. Postmenopausal women with low bone mass, on or off antiresorptive bone medications were randomly allocated, stratified on medication intake, to eight months of twice-weekly, supervised HiRIT (Onero™) or LiPBE (Buff Bones®). 3D hip software was used to analyse proximal femur DXA scans. Outcomes included femoral neck (FN) and total hip (TH), volumetric (e.g. vBMC, vBMD) and geometric (e.g. cortical thickness, cross-sectional area [CSA], section modulus [Z]) indices of bone strength. Data were analysed using analysis of variance. Scans of 102 women were examined: LiPBE, 43; HiRIT, 37; LiPBE-med, 11; HiRIT-med, 11. HiRIT improved TH trabecular vBMC and vBMD (3.1 ± 1.1% versus − 1.2 ± 1.2%, p = 0.008; and 1.5 ± 1.0% versus − 1.6 ± 1.2%, p = 0.042, respectively) and FN and TH total vBMC (2.0 ± 0.8% versus − 0.2 ± 0.7%, p = 0.032; and 0.7 ± 0.4% versus − 0.8 ± 0.6%, p = 0.032, respectively), compared to losses in LiPBE. HiRIT also increased Z while LiPBE did not (p = 0.035). The combination of HiRIT and medication achieved greater improvements in FN total and trabecular vBMD, total BMC, CSA and Z than HiRIT alone. HiRIT improved geometric parameters of proximal femur strength, while LiPBE exercise was largely ineffective. Medication may enhance some HiRIT effects. Findings suggest reduced hip fracture risk in response to HiRIT.Trial registration number ACTRN12617001511325.

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function in humans and the potential role of post-translational proteinmodification in this phenomenon. Therefore, the purpose of this study was to examine theeffect of in vivo fatigue on the phosphorylation status of sarcomeric proteins and contractileperformance of human single muscle fibers. METHODS: In two separate studies, seven healthyadults performed repeated knee extensions until task failure with their dominant leg.Immediately following, bilateral, percutaneous biopsy of the vastus lateralis muscle wasperformed on the fatigued and non-fatigued (control) limbs. Tissue was divided and portionswere blotted, snap frozen, and stored at -80°C until analysis by high resolution massspectrometry or prepared for single fiber mechanical analysis. Mass spec data were assessedusing edgeR while mechanical outcomes were assed via 2-way ANOVA using SPSS. RESULTS:Mass spectrometry confirmed differential phosphorylation of multiple residues in sarcomericproteins, including regulatory light chain and troponin I. We also observed phosphoenrichmentof myosin binding protein C (MyBP-C) and tropomyosin (β-Tm), and a reduction in titinphosphorylation. Mechanical analysis showed that fatigued fibers produced significantly lesspower (8.0 ± 6.2 mN/mm 2 ) than controls (5.9 ± 3.9 mN/mm 2 ; p=0.05). Differences in tension(p=0.11) or velocity (p=0.11) relative to non-fatigued fibers were not significant. No MHCisoform by fatigue interactions were observed. CONCLUSION: These data suggest fatiguingcontractions alter phosphorylation of select sarcomeric proteins and alter contractileperformance in isolated single muscle fibers regardless of intracellular environment, supportingthe notion that altered contractile protein function potentiates in vivo fatigue and maycontribute to longer-lasting contractile deficits.

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