Muscle mass and strength are key determinats of bone health. Falls and fragility fractures are associated with reduction in muscle mass with consequent impairment in physical function.
The deuterated creatine (D3Cr) dilution is a novel and interesting methodology that estimates total body creatinine for assessing the overall muscle mass. The D3-creatine is a stable isotope-labeled creatine that is ingested by patient. The D3-Cr and creatine are measured 3-6 days later on fasting morning urine samples by the HPLC/MS methodology. The use of an algorithm allows to calculate the total body pool of creatine that is considered as the creatine absorbed and diluted in the skeletal muscle and therefore as a reliable measure of muscle mass.
In a recent paper by Cawthon et al., the D3Cr dilution methodology is employed to assess muscle mass and explore its relationship with incident fragility fractures in a cohort of 1,363 older men from the MrOs study in a mean follow-up time of roughly 4 years and a half. Interestingly, fractured men had lower muscle mass as assessed by the D3Cr dilution methodology, and the lower was the D3Cr muscle mass quartile, the higher was the fracture incidence. Authors suggest that the D3Cr muscle mass may be useful to implement the algorithm currently employed in the fracture risk calculation and to eventually better identify higher risk patients. Their conclusion is driven also by the observation of a 1.8-fold and 1.4-fold higher risk of hip and major osteoporotic fractures, respectively, for any SD decrease in D3Cr muscle mass.
The interesting results of this study draw attention on several aspects of the complex relationship between bone and muscle. First, they suggest that there is an actual direct influence of muscle mass on skeletal fragility. Indeed, muscle function and physical performance did not completely mediated the association between D3Cr muscle mass and incident fractures in the study. Mechanisms associated with the interesting cross talk between bone and skeletal muscle, involving direct (eg myokines) and indirect effects, are not completely known. Future clinical research needs to focus on this topic and on the assessment of muscle mass and its influence on the main determinants of skeletal fragility, including bone mass, quality and strength.
Secondly, as the authors pointed out, further data from clinical studies will clarify whether or not the D3Cr muscle mass assessment has the potential of being included in the clinical diagnosis of sarcopenia with the aim of a more comprehensive assessment of this disorder.
Finally, the employment of this methodology in other classes of patients, as those with secondary osteoporosis, or in premenopausal/juvenile osteoporosis, will be interesting in the attempt of better identifying those at higher fracture risk and guide the therapeutic approach.