Increased bone resorption and impaired bone microarchitecture in short-term and extended high-fat diet–induced obesity

Abstract

Although obesity traditionally has been considered a condition of low risk for osteoporosis, this classic view has recently been questioned. The aim of this study was to assess bone microarchitecture and turnover in a mouse model of high-fat diet-induced obesity. Seven-week-old male C57BL/6J mice (n = 18) were randomized into 3 diet groups. One third (n = 6) received a low-fat diet for 24 weeks, one third was kept on an extended high-fat diet (eHF), and the remaining was switched from low-fat to high-fat chow 3 weeks before sacrifice (sHF). Serum levels of insulin, leptin, adiponectin, osteocalcin, and cross-linked telopeptides of type I collagen (CTX) were measured. In addition, bone microarchitecture was analyzed by micro-computed tomography; and lumbar spine bone density was assessed by dual-energy x-ray absorptiometry. The CTX, body weight, insulin, and leptin were significantly elevated in obese animals (sHF: +48%, +24%, +265%, and +102%; eHF: +43%, +52%, +761%, and +292%). The CTX, body weight, insulin, and leptin showed a negative correlation with bone density and bone volume. Interestingly, short-term high-fat chow caused similar bone loss as extended high-fat feeding. Bone volume was decreased by 12% in sHF and 19% in eHF. Bone mineral density was 25% (sHF) and 27% (eHF) lower when compared with control mice on low-fat diet. As assessed by the structure model index, bone microarchitecture changed from plate- to rod-like appearance upon high-fat challenge. Trabecular and cortical thickness remained unaffected. Short-term and extended high-fat diet-induced obesity caused significant bone loss in male C57BL/6J mice mainly because of resorptive changes in trabecular architecture.

Association of larger holes in the trabecular bone at the distal radius in postmenopausal women with type 2 diabetes mellitus compared to controls

“…The mechanism causing larger holes in the trabecular bone network at the radius in participants with type 2 DM is not fully understood. However, studies in rodent models of type 2 DM and in rodents fed high-fat diets have demonstrated a reduction in osteoblast recruitment and mineral apposition rate and an increase in osteoclastogenesis, resulting in an imbalance between bone formation and resorption (42,43). Cross-sectional findings in humans further support these data, as serum markers of bone formation, such as osteocalcin, are lower and markers of bone resorption, such as C-terminal telopeptide of type 1 collagen, are elevated in participants with type 2 DM (44,45).…”

Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights

“…This weight gain, seen in both young and aging mice, is associated with visceral adiposity, insulin resistance, and, in some instances, bone loss. (62,63) But other studies have shown that C57BL/6 mice on an HFD have higher marrow adipose tissue yet either normal or increased aBMD. (64,65) Moreover, rates of bone formation in mice fed an HFD are either normal (64) or are temporally increased followed by a significant decrease in bone turnover concurrent with development of obesity and glucose intolerance.…”

Type 1 diabetic bone loss is prevented by novel osteogenic factors

“…Impaired glucose tolerance is more severe in males than females [33]. The C57BL/6J mouse appears to have adverse effects on trabecular bone components [34], and recent evidence suggests that the effect of the high-fat diet is more pronounced in skeletally immature compared to skeletally mature mice [35][36][37]. Lower trabecular bone volumes are primary the result of increased osteoclast resorption as indicated by serum biomarkers and histomorphotometry [35][36][37], though bone formation is also decreased [38].…”

“…The C57BL/6J mouse appears to have adverse effects on trabecular bone components [34], and recent evidence suggests that the effect of the high-fat diet is more pronounced in skeletally immature compared to skeletally mature mice [35][36][37]. Lower trabecular bone volumes are primary the result of increased osteoclast resorption as indicated by serum biomarkers and histomorphotometry [35][36][37], though bone formation is also decreased [38]. Interestingly, recent data indicate that whereas body weight and fasting glucose levels can return to normal after a return to a normal diet, trabecular bone loss prior to skeletal maturity may not be recoverable without some other types of intervention [34].…”