Skeletal Muscle Mass Measurement May Predict Risk for Hip Fracture Among Older Men

Bone density indicates future fracture risk.
Bone density indicates future fracture risk.
A team of researchers investigated whether low muscle mass as assessed via D3-creatine dilution may be associated with risk of fracture.

Among older men, low D3-creatine dilution (D3Cr) muscle mass/weight was observed to be associated with increased risk for hip fractures. These findings were published in the Journal of Bone and Mineral Research.

The Osteoporotic Fractures in Men (MrOS) study was a multicenter cohort study conducted between 2000 and 2002. Men aged 65 years and older without bilateral hip replacements were evaluated for baseline bone health. Between 2014 and 2016, survivors of the original MrOS cohort were invited to be re-evaluated for this analysis. Study participants (N=1363) were assessed for incidence of hip fracture, bone mineral density (BMD) via dual-energy x-ray absorptiometry (DXA) scan, D3Cr muscle mass/weight, and 10-year Fracture Risk Assessment Tool (FRAX) risk. Determination of D3Cr was accomplished by urine creatine concentration 3 to 6 days following a 30-mg dose of labeled creatine.

A total of 13.2% of men had at least 1 clinical fracture. Fractures were nonspine fractures (n=153), major osteoporotic fractures (n=85), and hip fractures (n=40).

Participants with (n=40) and without (n=1326) incident hip fracture had a mean age of  86.0±4.6 and 84.1±4.0 years (P =.004), body mass index (BMI) was 25.8±3.4 and 26.8±3.7 kg/m2, D3Cr muscle mass/weight was 0.28±0.04 and 0.31±0.05 (P =.004), and 82.5% and 60.2% had a previous fracture (P =.004), respectively.

After adjusting for height and weight, D3Cr muscle mass/weight was correlated with femoral neck BMD (r, 0.10; P <.001) and total hip BMD (r, 0.14; P <.001).

Stratified by quartile of D3Cr muscle mass/weight, an inverse relationship was reported between hip and major osteoporotic fractures. Men in the lowest quartile had higher rates of hip fractures (9.0 vs 2.4 per 1000 person-years [py]) and major osteoporotic fractures (19.0 vs 9.6 per 1000 py) compared with the highest quartile, respectively. A negative relationship between D3Cr muscle mass/weight and any fracture (37.3 vs 23.2 per 1000 py) or nonspine fracture (29.5 vs 18.1 per 1000 py) was not observed; however, men in the lowest quartile still had increased fracture rates compared with the highest quartile, respectively.

In a multivariate model, after adjusting for age, femoral neck BMD, FRAX, and fall history, for every standard deviation (SD) decrease in D3Cr muscle mass/weight, the risk for hip fracture increased by 1.8-fold (hazard ratio [HR], 1.75; 95% CI, 1.22-2.50 per SD), the rate for osteoporotic fracture increased by 1.4-fold (HR, 1.37; 95% CI, 1.08-1.74 per SD), the rate for nonspine fracture increased by 1.2-fold (HR, 1.21; 95% CI, 1.02-1.43 per SD), and the rate for any clinical fracture increased by 1.2-fold (HR, 1.22; 95% CI, 1.04-1.43 per SD).

After accounting for muscle function and physical performance, the significant associations were attenuated; however, the relationship with hip and major osteoporotic fractures trended toward significance.

This study may have been limited by not adjusting for physical activity.

This study found a relationship between low D3Cr muscle mass/weight and fracture risk among older men. Additional research is needed to determine whether the evaluation of D3Cr muscle mass/weight may have clinical utility.

Disclosure: Multiple authors declared affiliations with the biotech or pharmaceutical industries. Please refer to the original article for a full list of disclosures.


Cawthon PM, Peters KE, Cummings SR, et al; the Osteoporotic Fractures in Men (MrOS) Study Research Group. Association between muscle mass determined by d3-creatine dilution and incident fractures in a prospective cohort study of older men. J Bone Miner Res. Published online March 6, 2022. doi:10.1002/jbmr.4505