Application of the D3 -creatine muscle mass assessment tool to a geriatric weight loss trial: A pilot study.

BACKGROUND: Traditionally, weight loss (WL) trials utilize dual energy X-ray absorptiometry (DXA) to measure lean mass. This method assumes lean mass, as the sum of all non-bone and non-fat tissue, is a reasonable proxy for muscle mass. In contrast, the D3 -creatine (D3 Cr) dilution method directly measures whole body skeletal muscle mass, although this method has yet to be applied in the context of a geriatric WL trial. The purpose of this project was to (1) describe estimates of change and variability in D3 Cr muscle mass in older adults participating in an intentional WL intervention and (2) relate its change to other measures of body composition as well as muscle function and strength. METHODS: The INVEST in Bone Health trial (NCT04076618), used as a scaffold for this ancillary pilot project, is a three-armed, 12-month randomized, controlled trial designed to determine the effects of resistance training or weighted vest use during intentional WL on a battery of musculoskeletal health outcomes among 150 older adults living with obesity. A convenience sample of 24 participants (n = 8/arm) are included in this analysis. At baseline and 6 months, participants were weighed, ingested a 30 mg D3 Cr tracer dose, provided a fasted urine sample 3-6 days post-dosage, underwent DXA (total body fat and lean masses, appendicular lean mass) and computed tomography (mid-thigh and trunk muscle/intermuscular fat areas) scans, and performed 400-m walk, stair climb, knee extensor strength, and grip strength tests. RESULTS: Participants were older (68.0 ± 4.4 years), mostly White (75.0%), predominantly female (66.7%), and living with obesity (body mass index: 33.8 ± 2.7 kg/m2 ). Six month total body WL was -10.3 (95% confidence interval, CI: -12.7, -7.9) kg. All DXA and computed tomography-derived body composition measures were significantly decreased from baseline, yet D3 Cr muscle mass did not change [+0.5 (95% CI: -2.0, 3.0) kg]. Of muscle function and strength measures, only grip strength significantly changed [+2.5 (95% CI: 1.0, 4.0) kg] from baseline. CONCLUSIONS: Among 24 older adults, significant WL with or without weighted vest use or resistance training over a 6-month period was associated with significant declines in all bioimaging metrics, while D3 Cr muscle mass and muscle function and strength were preserved. Treatment assignment for the trial remains blinded; therefore, full interpretation of these findings is limited. Future work in this area will assess change in D3 Cr muscle mass by parent trial treatment group assignment in all study participants.

Strategies to reduce the onset of sleeve gastrectomy associated bone loss (STRONG BONES): Trial design and methods.

Background: Despite recognized improvements in obesity-related comorbidities, mounting evidence implicates surgical weight loss in the onset of skeletal fragility. Sleeve gastrectomy (SG) is the most commonly performed bariatric procedure and is associated with 3-7% axial bone loss in the year following surgery. Bisphosphonates are FDA-approved medications for the prevention and treatment of age-related bone loss and may represent a strategy to reduce bone loss following SG surgery. Methods: The Strategies to Reduce the Onset of Sleeve Gastrectomy Associated Bone Loss (STRONG BONES) trial (NCT04922333) is designed to definitively test whether monthly administration of the bisphosphonate, risedronate, for six months can effectively counter SG-associated bone loss. Approximately 120 middle-aged and older (≥40 years) SG patients will be randomized to six months of risedronate or placebo treatment, with skeletal outcomes assessed at baseline, six, and 12-months post-surgery. The primary outcome of the trial is 12-month change in total hip areal bone mineral density (aBMD), measured by dual energy x-ray absorptiometry (DXA). This will be complemented by DXA-acquired aBMD assessment at other skeletal sites and quantitative computed tomography (QCT) derived changes in bone quality. Change in muscle mass and function will also be assessed, as well as biomarkers of bone health, turnover, and crosstalk, providing mechanistic insight into intervention-related changes to the bone-muscle unit. Discussion: Results from the STRONG BONES trial have the potential to influence current clinical practice by determining the ability of bisphosphonate use to mitigate bone loss and concomitant fracture risk in middle-aged and older SG patients.

Characterizing thoracic morphology variation to develop representative 3D models for applications in chest trauma.

BACKGROUND: Rib fracture(s) occurs in 85% of blunt chest trauma cases. Increasing evidence supports that surgical intervention, particularly for multiple fractures, may improve outcomes. Thoracic morphology diversity across ages and sexes is important to consider in the design and use of surgical intervention devices in chest trauma. However, research on non-average thoracic morphology is lacking. METHODS: The rib cage was segmented from patient computed tomography (CT) scans to create 3D point clouds. These point clouds were uniformly oriented and chest height, width, and depth were measured. Size categorization was determined by grouping each dimension into small, medium, and large tertiles. From small and large size combinations, subgroups were extracted to develop thoracic 3D models of the rib cage and surrounding soft tissue. RESULTS: The study population included 141 subjects (48% male) ranging from age 10-80 with ∼20 subjects/age decade. Mean chest volume increased with age by 26% from the age groups 10-20 to 60-70, with 11% of this increase occurring between the youngest groups of 10-20 and 20-30. Across all ages, chest dimensions were ∼10% smaller in females and chest volume was highly variable (SD: ±3936.5 cm3). Representative thoracic models of four males (ages 16, 24, 44, 48) and three females (ages 19, 50, 53) were developed to characterize morphology associated with combinations of small and large chest dimensions. CONCLUSIONS: The seven models developed cover a broad range of non-average thoracic morphologies and can serve as a basis for informing device design, surgical planning, and injury risk assessments.

Age-based differences in the disability of spine injuries in pediatric and adult motor vehicle crash occupants.

OBJECTIVE: The objective was to develop a disability-based metric for quantifying disability rates as a result of motor vehicle crash (MVC) spine injuries and compare functional outcomes between pediatric and adult subgroups. METHODS: Disability rate was quantified using Functional Independence Measure (FIM) scores within the National Trauma Data Bank-Research Data System for the top 95% most frequent Abbreviated Injury Scale (AIS) 3 spine injuries (14 unique injuries). Pediatric (7-18 years), young adult (19-45 years), middle-aged adult (46-65 years), and older adult (66+ years) MVC occupants with FIM scores available and at least one of the 14 spine injuries were included. FIM scores of 1 or 2 at time of discharge were used to define disability and correspond to full functional or modified dependence in self-feeding, locomotion, and/or verbal expression. Disability rate was evaluated on a per injury basis for each AIS 3 spine injury and calculated as the proportion of cases associated with disability (i.e. FIM of 1 or 2) out of the total cases of that particular injury. Disability rates were calculated with and without the exclusion of cases with severe co-injuries (AIS 4+) to minimize bias from additional non-spinal injuries that could have contributed to disability. Associations between adjusted disability rates and existing mortality rates were investigated. RESULTS: Locomotion impairment alone was the most frequent disability type for the top 14 AIS 3 spine injuries (7 cervical, 4 thoracic, and 3 lumbar) across all age groups and spine regions. Adjusted and unadjusted disability rates ranged from 0-69%. Adjusted disability rates increased with age: 14.8 ± 10% (mean ± SD) in pediatrics to 16.2 ± 6.6% (young adults), 29.2 ± 10.9% (middle-aged adults), and 45.0 ± 12.2% (older adults). Among all adult populations, adjusted mortality and disability rates were positively correlated (R2>0.24), with disability rates consistently greater than corresponding mortality rates. CONCLUSIONS: Older adults had significantly greater disability rates associated with MVC spine injuries across all spinal regions. MVC disability rates for pediatrics were considerably lower. Overall, rates of mortality were significantly lower than rates of disability. The adjusted disability rates developed can supplement existing injury metrics by accounting for age- and location-specific functional implications of MVC spine injuries.

Incorporating Nutrition, Vests, Education, and Strength Training (INVEST) in Bone Health: Trial Design and Methods.

BACKGROUND: Achievement of 5-10% weight loss (WL) among older adults living with obesity considerably improves prognosis of health-related outcomes; however, concomitant declines in bone mineral density (BMD) limit overall benefit by increasing fracture risk. Declines in mechanical loading contribute to WL-associated BMD loss, with pilot data signaling the addition of external weight replacement (via weighted vest use) during intentional WL mitigates bone loss at weight bearing sites to a similar degree as resistance exercise training (RT). Definitive data in support of weighted vest use as a potential strategy to mitigate WL-associated bone loss in this population are needed. METHODS: In the Incorporating Nutrition, Vests, Education, and Strength Training (INVEST) in Bone Health trial (NCT04076618), 192 older adults (60-85 years) who are overweight (BMI ≥ 27 kg/m2) with at least one obesity-related risk factor or obese (BMI = 30-40 kg/m2) will be randomly assigned to participate in one of three 12-month intervention groups: WL alone, WL + weighted vest use (WL + VEST), or WL + RT. The primary aim is to determine the effects of WL + VEST compared to WL alone and WL + RT on indicators of bone health and subsequent fracture risk. DISCUSSION: Determining effective, translatable strategies that minimize bone loss during intentional WL among older adults holds public health potential. The INVEST in Bone Health trial offers an innovative approach for increasing mechanical stress during intentional WL in the absence of RT. If successful, findings from this study will provide evidence in support of a scalable solution to minimize bone loss during intentional WL among older adults with obesity.