Circulating Carboxylated Osteocalcin Correlates With Skeletal Muscle Mass and Risk of Fall in Postmenopausal Osteoporotic Women

Abstract

BackgroundBone and skeletal muscle represent a single functional unit. We cross-sectionally investigated body composition, risk of fall and circulating osteocalcin (OC) isoforms in osteoporotic postmenopausal women to test the hypothesis of an involvement of OC in the bone-muscle crosstalk.Materials and MethodsTwenty-nine non-diabetic, non-obese, postmenopausal osteoporotic women (age 72.4 ± 6.8 years; BMI 23.0 ± 3.3 kg/m2) underwent to: 1) fasting blood sampling for biochemical and hormone assays, including carboxylated (cOC) and uncarboxylated (uOC) osteocalcin; 2) whole-body dual energy X-ray absorptiometry (DXA) to assess total and regional body composition; 3) magnetic resonance imaging to determine cross-sectional muscle area (CSA) and intermuscular adipose tissue (IMAT) of thigh muscles; 4) risk of fall assessment through the OAK system.ResultsAppendicular skeletal muscle index (ASMMI) was low in 45% of patients. Forty percent got a low OAK score, consistent with moderate-severe risk of fall, which was predicted by low legs lean mass and increased total fat mass. Circulating cOC levels showed significantly correlated with βCTx-I, lean mass parameters including IMAT, and OAK score. Fractured and unfractured women did not differ for any of the analyzed parameters, though cOC and uOC positively correlated with legs lean mass, OAK score and bone markers only in fractured women.ConclusionsData supported the relationship between OC and skeletal muscle mass and function in postmenopausal osteoporotic women. Serum cOC, but not uOC, emerges as mediator in the bone-muscle crosstalk. Circulating cOC and uOC levels may be differentially regulated in fractured and unfractured osteoporotic women, suggesting underlying differences in bone metabolism.

Interrelationship among thigh intermuscular adipose tissue, cross-sectional area, muscle strength, and functional mobility in older subjects

“…Regarding muscles, aging is associated with a decline in skeletal muscle mass and function, causing an alteration of strength, physical performance, and movement. [7][8][9] Estimates for the total decline in the muscle mass between 40 and 80 years of age range from 30% to 50%, and the annual decline in functional capacity is reported to be 1% to 2% after the age of 50 increasing to 3% after 60 years. [10] This process begins sooner in women than in men, when comparing levels of isometric strength of the same muscle group.…”

Osteocalcin modulates parathyroid cell function in human parathyroid tumors

“…Interestingly, at variance with data reported in mouse models, where GluOC showed endocrine function ( 46 ), our data obtained both in human primary tumor cell and in human cell line cultures, indicated GlaOC as the bioactive molecule able to more consistently elicit modulation of intracellular signaling pathways and of gene expression. Differences observed between mice, where the hormone function is evident for GluOC, and humans, where GlaOC may act as modulator of the parathyroid function in adenomatous glands and of the skeletal muscle ( 47 ), may be related to the different carboxylation status: OC is γ-carboxylated on glutamic acids (Glu) 13, 17 and 20 of protein in mouse, and on Glu 17, 21 and 24 in humans ( 48 ).…”

Association between skeletal muscle mass index and falls in patients with functional impairment

“…Vitale et al 20 reported that factors associated with risk of falls were not SMI, but rather increased intermuscular adipose tissue. While SMI is a measure of muscle quantity, intramuscular adipose tissue and muscle fibrosis are those of muscle quality and can be evaluated by several devices including computed tomography, magnetic resonance imaging, and ultrasonography 22–24 . The decline in muscle quality is associated with poor muscle strength and physical performance in older adults 25,26 .…”

“…While SMI is a measure of muscle quantity, intramuscular adipose tissue and muscle fibrosis are those of muscle quality and can be evaluated by several devices including computed tomography, magnetic resonance imaging, and ultrasonography. [22][23][24] The decline in muscle quality is associated with poor muscle strength and physical performance in older adults. 25,26 Yamada et al 23 reported that not only lower muscle quantity but also muscle quality decreases led to higher incidents of falls.…”