The main objective of the proposed study is to definitively test whether risedronate use
can effectively counter SG associated bone loss. To do this, we propose to randomize 120
middle-aged and older (≥40 years) SG patients to six months of risedronate or placebo
treatment, with musculoskeletal outcomes assessed at baseline, six, and 12 months. Due to
its robust change following SG and clinical utility in predicting fracture, our primary
outcome is change in total hip areal (a)BMD measured by dual energy x-ray absorptiometry
(DXA). This will be complemented by DXA-acquired aBMD assessment at other skeletal sites
and appendicular lean mass, as well as quantitative computed tomography (QCT) derived
changes in bone (volumetric BMD, cortical thickness, and strength) and muscle (cross
sectional area, fat infiltration) at the hip and spine, and high-resolution peripheral
quantitative computed tomography (HR-pQCT) derived changes in bone microarchitecture,
density, and strength at the tibia and radius - allowing for novel assessment of
intervention effectiveness on several state-of-the-art bioimaging metrics. Select
measures of muscle function (fast 400-m walk, stair climb, knee extensor strength) are
also included as proxies of fall risk. Finally, biomarkers of bone turnover (CTX, P1NP),
bone-muscle crosstalk (TGF-β, RANKL, myostatin), and gut hormones (ghrelin, PYY, GLP-1)
will be assessed in a tertiary aim, providing mechanistic insight into
intervention-related changes to the bone-muscle unit. Thus, we aim to:
Aim 1: Determine the effect of risedronate compared to placebo on 12-month change from
baseline in total hip aBMD following SG. We hypothesize that participants assigned to
risedronate will better preserve total hip aBMD than participants assigned to placebo.
Aim 2: Determine the effects of risedronate compared to placebo on 12-month change from
baseline in DXA-acquired aBMD at additional skeletal sites (femoral neck, lumbar spine,
distal radius) and appendicular lean mass; QCT-derived measures of bone (volumetric BMD,
cortical thickness, and strength) and muscle (cross sectional area, density, fat
infiltration) at the hip and spine; HR-pQCT derived measures of bone microarchitecture,
density, and strength at the tibia and radius; and muscle function (fast 400-m walk,
stair climb, knee extensor strength) following SG. We hypothesize that participants
assigned to risedronate will yield greater preservation/improvement in all secondary
metrics than participants assigned to placebo.
Aim 3: Investigate the impact of treatment group assignment on biomarkers of bone
turnover, bone-muscle crosstalk, and gut hormones to elucidate mechanisms underlying
change in bone and muscle quantity and quality.