Weight Loss With Risedronate for Bone Health

This pilot study is a RCT, involving 24 participants randomized to Risedronate or placebo capsules for 24 weeks. All subjects planning a sleeve gastrectomy (SG) procedure will be approached during their pre-surgical evaluation for possible participation in the study. Eligible participants will be referred onto the study coordinator to read/sign an IRB-approved informed consent prior to enrollment.

Two in-person baseline assessment visits \[baseline visit 1 (BV1), baseline visit 2 (BV2)\] occurring 1-6 weeks prior to surgery, and two in-person follow up assessment visits \[follow up visit 1 (FV1) and follow up visit 2 (FV2)\] occurring ±2 weeks from their 23-week post-surgery date will be conducted, as well as monthly medication compliance reminders and adverse event reporting via phone. Optional additional exploratory assessments include CT-derive bone health and blood-based biomarkers, as well as 12-month DXA, CT, and blood assessments. The Wake Forest WMC, under the direction of Drs. Ard and Fernandez, will serve as a source of recruitment for potential study participants.

• Risedronate Sodium 150 MG (Drug), also known as Code A: Subjects randomized to the Risedronate group will take a 150 mg capsule of oral Risedronate once every 4 weeks for 24 weeks (6 doses), beginning 1 week prior to surgery and dispensed in blinded capsules from the WFSM research pharmacy.
• Placebo (Other), also known as Code B: Participants randomized to the placebo group will receive 150 mg placebo capsule once every 4 weeks for 24 weeks (6 doses), beginning 1 week prior to surgery and dispensed in blinded capsules from the WFSM research pharmacy.

Primary outcomes

• Number of Enrolled Participants That Completed All 24 Week Procedures [24 weeks]

Secondary outcomes

• Fat Pounds [24 weeks]: Duel-energy x-ray absorptiometry (DXA)-Acquired Measure--Fat pounds portion of Total body composition
• Lean Pounds [24 weeks]: Duel-energy x-ray absorptiometry (DXA)-Acquired Measure--Lean pounds portion of Total body composition
• Total Change in Femoral Neck Hip Density [Baseline and 24 weeks]: Duel-energy x-ray absorptiometry (DXA)-Acquired Measure for Total Hip Density measured in g/cm\^2
• Total Change in Lumbar Spine Density [Baseline and 24 weeks]: Duel-energy x-ray absorptiometry (DXA)-Acquired Measure for Lumbar Spine Density measured in g/cm\^2
• Duel-energy X-ray Absorptiometry (DXA)-Acquired Measure for Ultradistal Radius (or UD Radius) Density [24 weeks]: Total change in ultradistal radius density measure in g/cm\^2
• Trabecular Bone Score (TBS) [24 weeks]: TBS of the lumbar spine measured by two dimensional (2D) variogram acquired through duel-energy x-ray absorptiometry (DXA). Trabecular bone score is a unitless index of bone microarchitecture. A high TBS value means that bone microarchitecture is dense and well connected, with little space between trabeculae. The following normal range for TBS values in postmenopausal women has been proposed: TBS >=1.350 is considered to be normal; TBS between 1.200 and 1.350 is considered to be consistent with partially degraded microarchitecture; and TBS <=1.200 defines degraded microarchitecture

Sex: All, ages: 40 Years to 79 Years, accepts healthy volunteers

Inclusion Criteria

* Subjects planning a sleeve gastrectomy procedure
* 40-79 yrs of age
* Willingness to provide informed consent
* Agreement to all study procedures and assessments

Exclusion Criteria

* Age <40 years
* Baseline weight >450 pounds
* Chronic anti-reflux treatment
* History of medical disorders known to affect bone metabolism
* Use of bone-active medications
* Known allergy to Risedronate

Participant flow

Outcome results

• Number of Enrolled Participants That Completed All 24 Week Procedures (Primary), Count of participants, Participants: Risedronate 8; Placebo 13
• Fat Pounds (Secondary), Mean, pounds: Risedronate 45.6 (41.8 to 49.4); Placebo 40.6 (37.9 to 43.4) (p 0.048)
• Lean Pounds (Secondary), Mean, pounds: Risedronate 50.4 (49.1 to 51.8); Placebo 50.7 (49.7 to 51.7) (p 0.745)
• Total Change in Femoral Neck Hip Density (Secondary), Mean, g/cm^2: Risedronate -0.028 (-0.049 to -0.006); Placebo -0.047 (-0.063 to -0.030) (p 0.163)
• Total Change in Lumbar Spine Density (Secondary), Mean, g/cm^2: Risedronate 0.028 (-0.006 to 0.063); Placebo -0.029 (-0.054 to -0.004) (p 0.013)
• Duel-energy X-ray Absorptiometry (DXA)-Acquired Measure for Ultradistal Radius (or UD Radius) Density (Secondary), Mean, g/cm^2: Risedronate -0.002 (-0.027 to 0.023); Placebo -0.016 (-0.036 to 0.004) (p 0.337)
• Trabecular Bone Score (TBS) (Secondary), Mean, score on a scale: Risedronate 1.478 (1.413 to 1.543); Placebo 1.485 (1.436 to 1.533) (p 0.860)

Adverse events

Time frame: baseline through 12 months

Serious adverse events by term

Other adverse events by term

• Results publication: Swafford AA, Ard JD, Beavers DP, Gearren PC, Fernandez AZ, Ford SA, Greene KA, Kammire DE, Nesbit BA, Reed KK, Weaver AA, Beavers KM. Risedronate to Prevent Bone Loss After Sleeve Gastrectomy: Study Design and Feasibility Report of a Pilot Randomized Controlled Trial. JBMR Plus. 2020 Oct 2;4(10):e10407. doi: 10.1002/jbm4.10407. eCollection 2020 Oct. PMID 33103032

• Informed Consent Form (PDF, 2020-06-02)
• Study Protocol (PDF, 2020-10-01)
• Statistical Analysis Plan (PDF, 2020-12-29)

• Kristen M Beavers, PhD, Principal investigator, Wake Forest University