To assess differential features of marrow adiposity between postmenopausal women with osteoarthritis and osteoporosis using water/fat MRI :

The classical view of the pathogenesis of osteoarthritis (OA) is that subchondral sclerosis is associated with, and perhaps causes, age-related joint degeneration. Recent observations have demonstrated that OA is associated with early loss of bone owing to increased bone remodelling, followed by slow turnover leading to densification of the subchondral plate and complete loss of cartilage. Subchondral densification is a late event in OA that involves only the subchondral plate and calcified cartilage; the subchondral cancellous bone beneath the subchondral plate may remain osteopenic. In experimental models, inducing subchondral sclerosis without allowing the prior stage of increased bone remodelling to occur does not lead to progressive OA. Therefore, both early-stage increased remodelling and bone loss, and the late-stage slow remodelling and subchondral densification are important components of the pathogenetic process that leads to OA. The apparent paradoxical observations that OA is associated with both increased remodelling and osteopenia, as well as decreased remodelling and sclerosis, are consistent with the spatial and temporal separation of these processes during joint degeneration. This Review provides an overview of current knowledge on OA and discusses the role of subchondral bone in the initiation and progression of OA. A hypothetical model of OA pathogenesis is proposed.

To use proton magnetic resonance spectroscopy ((1)H-MRS) to evaluate vertebral marrow fat, and to determine whether bone density correlates with fat content and fat unsaturation levels in postmenopausal women. Fifty-three women (mean age = 70 years) underwent dual energy x-ray absorptiometry and (1)H-MRS, and 12 young female controls (mean age = 28 years) underwent (1)H-MRS of the lumber spine. Water and lipid peak amplitudes were measured to calculate fat content and fat unsaturation index. Spearman's correlation tests and a t-test comparison of means were applied. (1)H-MRS was successful in 15 normal, 15 osteopenic, and 20 osteoporotic subjects, and in all controls. Marrow fat content was significantly elevated in osteoporotic (65.5% +/- 10%) and osteopenic (63.5% +/- 9.3%) subjects compared to normal subjects (56.3% +/- 11.2%) and young controls (29% +/- 9.6%). The fat unsaturation index was significantly decreased in osteoporotic (0.091 +/- 0.013) and osteopenic (0.097 +/- 0.014) subjects compared to normal subjects (0.114 +/- 0.016) and young controls (0.127 +/- 0.031). A good inverse correlation was observed between the fat content and the unsaturation index (r(s) = -0.53, P < 0.0001). Osteoporosis is associated with increased marrow fat. As marrow fat increases, saturated lipids appear to increase preferentially to unsaturated lipids. (c) 2005 Wiley-Liss, Inc.

Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS2-12, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59% increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50%. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-gamma2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages.