More body fat linked to lower bone density, especially in men

High levels of body fat are associated with a lower bone mineral density, with the association more pronounced in men compared with women, according to study data published in The Journal of Clinical Endocrinology & Metabolism.

“While higher BMI is generally associated with higher bone density, our study demonstrates that lean and fat mass affect bone density differently and that obesity is not a guarantee against osteoporosis,” Rajesh K. Jain, MD, assistant professor in the section of endocrinology, diabetes and metabolism and director of the endocrinology fellowship program at the University of Chicago Medicine, told Healio. “Patients with obesity should still undergo recommended bone density screening, especially if they have other risk factors, such as older age, previous fracture, family history or steroid use.”

Jain is an assistant professor in the section of endocrinology, diabetes and metabolism and director of the endocrinology fellowship program at the University of Chicago Medicine

Jain and colleagues analyzed data from 10,814 adults aged 20 to 59 years who participated in the National Health and Nutrition Examination Survey from 2011 to 2018 and underwent a total body DXA scan. T-scores were calculated to determine total body BMD. Lean mass index and fat mass index were calculated to assess the effects of body composition on BMD.

After adjusting for age, sex, race and ethnicity, height, smoking status, lean mass index and fat mass index, every 1 kg/m² of lean mass index was associated with a 0.19 higher total body BMD T-score (P < .001). Conversely, each 1 kg/m² increase in fat mass index was associated with a 0.1 decrease in BMD T-score (P < .001).

The association between fat mass index and BMD T-score differed for men and women. Women had a BMD T-score decrease of 0.08 points for every 1 kg/m² increase in fat mass index, whereas men had a 0.13 lower BMD T-score with every 1 kg/m² increase in fat mass index (P for interaction < .001). The association between fat mass index and BMD T-score did not differ by age group. For lean mass index, Mexican American adults had a lower BMD T-score increase of 0.16 for each 1 kg/m² increase compared with a 0.21 BMD T-score increase for each 1 kg/m² for white adults (P for interaction = .004). There were no other differences observed between race and ethnicity groups.

“Unfortunately, body composition is not a routine clinical measurement, so we rarely know what a patient’s body fat or body lean mass is,” Jain said. “Factors that correlate with high body fat and low lean mass are often associated with osteoporosis or fractures, and their presence should prompt clinicians to consider osteoporosis screening. This includes, for example, the presence of diabetes or poor performance on physical activity measures, such as grip strength.”

Jain said future research should examine the effects that weight loss may have on BMD.

“In general, weight loss has been associated with bone loss and fractures, but this study suggests the type of weight loss — lean vs. fat mass — may be important in determining if or how much bone loss occurs,” Jain said.

For more information:

Rajesh K. Jain, MD, can be reached at rjain2@medicine.bsd.uchicago.edu.

PERSPECTIVE

Mone Zaidi, MD, PhD, MBA, MACP, FRCP

Over the past two decades, we have worked on the idea that pituitary hormones have diverse functions beyond the unitary actions that appear traditionally in endocrine textbooks. We found, for the first time, that thyroid-stimulating hormone and follicle-stimulating hormone have direct actions on bone. The implication of these studies was that low TSH and high follicle-stimulating hormone levels in hyperthyroidism and after menopause likely contribute to the bone loss hitherto attributed solely to high thyroid hormone and low estrogen levels, respectively (Abe E, et al. Cell. 2003;doi:10.1016/s0092-8674(03)00771-2). 

Correlative studies in cohorts across the globe have shown strong associations between serum TSH or follicle-stimulating hormone, markers of bone remodeling, bone mineral density and fracture risk, independently of thyroxine or estrogen. Focusing on the effects of follicle-stimulating hormone, we developed a targeted follicle-stimulating hormone blocking antibody that prevented bone loss in mouse models (Zhu LL, et al. Proc Natl Acad Sci U S A. 2012;doi:10.1073/pnas.1212806109). Intriguingly, the follicle-stimulating hormone blocking antibody also reduced body fat and converted white adipose tissue to thermogenic beige adipose tissue (Liu X, et al, Nature. 2017;doi:10.1038/nmeth.4436) and, in a separate study, prevented cognitive decline and Alzheimer-like neuropathology in mouse models (Xiong, et al, Nature, 2022; in press).

Our humanized monoclonal follicle-stimulating hormone blocking antibody replicates these actions and has shown promise in preclinical studies toward first-in-human clinical trials in the very near future. Our admittedly ambitious premise is to treat osteoporosis, obesity and neurodegeneration with a single drug.

Mone Zaidi, MD, PhD, MBA, MACP, FRCP

Professor of Medicine and Pharmacological Sciences

Director, Center for Translational Medicine and Pharmacology

Director, Mount Sinai Bone Program

Icahn Sinai School of Medicine at Mount Sinai