Adding bone microarchitecture and strength measures to the STRONG BONES randomized trial examining risedronate use to mitigate bone loss after bariatric surgery - PROJECT SUMMARY Bariatric surgery is increasingly used to treat severe obesity and related comorbidities. However, clinical practice guidelines now recognize associated skeletal consequences, as mounting evidence implicates surgical weight loss in the onset of skeletal fragility. To address this, the randomized controlled trial, Strategies to Reduce the Onset of Sleeve Gastrectomy Associated Bone Loss (STRONG BONES; U01AR080969) is testing if the bisphosphonate, risedronate (a first-line osteoporosis drug), can effectively counter bone loss secondary to the most common bariatric surgical procedure, sleeve gastrectomy (SG). This trial is randomizing 120 SG patients (ages≥40) to 6 months of risedronate or placebo treatment, and assessing skeletal changes via dual energy x- ray absorptiometry (DXA), computed tomography (CT), and blood-based biomarkers at baseline, 6, and 12 months; yet, these modalities are not sufficient to measure bone microstructure changes that are expected with surgical weight loss and bisphosphonate treatment. The proposed ancillary study leverages the patient cohort, infrastructure, and data of the parent STRONG BONES trial, and enhances its scientific value by adding high- resolution peripheral quantitative computed tomography (HRpQCT) imaging to assess interventional effects on bone microarchitecture, density, and strength of the tibia and radius. HRpQCT is the only in vivo image modality with sufficient resolution (61µm) to assess trabecular and cortical microarchitecture. Using longitudinal HRpQCT imaging and micro-finite element (microFE) analysis of bone strength, we can pinpoint local areas of dynamic bone formation or resorption and examine the mechanoregulation of this bone remodeling. The ancillary study will add HRpQCT measures of the STRONG BONES participants, with four HRpQCT scans (distal tibia and radius; diaphyseal tibia and radius) per visit (baseline, 6 and 12 months). Building on the parent trial, this ancillary study is a timely, efficient, and cost-effective means to definitively test the scientific premise that risedronate can attenuate deterioration of bone microarchitecture, density, and strength secondary to SG. Specific Aims are to: (1) Determine the effect of risedronate vs. placebo on 12-month change in microFE-derived bone strength (failure load) of the tibia and radius following SG. (2) Determine the effect of risedronate following SG on 12-month change in HRpQCT-acquired trabecular and cortical bone mineral density and microarchitecture (e.g., trabecular number, spacing; cortex thickness, porosity). (3) Investigate the localized remodeling and mechanoregulation of bone in the microenvironment, and the associations of HRpQCT metrics with other skeletal outcomes obtained in the parent study [DXA, CT, and bone turnover/tissue-crosstalk biomarkers] to elucidate biological mechanisms underlying SG-associated bone loss and potential counteractant effects of risedronate. Definitive data supporting use of an existing, cost-effective, and safe medication to offset rapid degradation of bone microstructure after SG has the potential to shift current clinical practice paradigms, and offer mechanistic insight on the biology of SG-associated bone loss and risedronate as a treatment option to counteract microstructural tissue damage.
