Non traumatic osteonecrosis of the femoral head is associated with low bone mass.

OBJECTIVE: Osteoporosis (OP) and osteonecrosis of the femoral head (ONFH) share common clinical and pathophysiological features we sought to determine whether ONFH was associated with an increased prevalence of OP and whether the increased prevalence of OP was related to the stage of ONFH at diagnosis. METHODS: We included 243 patients with ONFH and 399 age and sex-matched healthy controls. Data was gathered including demography, risk factors, ARCO staging of ONFH and bone mineral density (BMD). RESULTS: Overall, BMD (defined by the T-score) was significantly lower in the ONFH group at both the femoral head (-0.96±1.11) and the lumbar spine (-1.22±1.47) compared to the control group (-0.55±0.97 and -0.73±1.31) (p<0.01). The ONFH group depicted a significantly higher proportion of osteopenia (50.39% vs 40.87%, p=0.027) and of OP (18.78% vs 7.33%, p<0.001) relative to the control group. Stage 1 and 2 ONFH patients (53.86%, p=0.0203; OR=1.54 (95% CI: [1.04; 2.29])) were at a higher risk of osteopenia than the control group (40.88%), but not stages 3 or 4 (48.47%, p=0.2569; OR=1.27 (95% CI: [0.78; 2.06]). Patients with stage 3 or 4 ONFH (25.31%, p<0.001; OR=3.93 (95% CI: [1.63; 10.96])) were at a higher risk of osteoporosis than patients in the stage 1 and 2 ONFH (7.24%), and compared to the control group (7.33%, adj. p-value<0.001; OR=4.89 (95% CI: [2.77; 8.76]). CONCLUSIONS: Non-traumatic osteonecrosis of the femoral heads is associated with low bone mineral density. This study showed that fractural stages ONFH were associated with a 5-fold risk of osteoporosis.

Osteonecrosis of the Femoral Head: Lipotoxicity Exacerbation in MSC and Modifications of the Bone Marrow Fluid.

Osteonecrosis of the femoral head (ON) is a multifactorial bone disease that can evolve to a progressive destruction of the hip joint. Different pathogenic processes have been proposed, among them, an increase of bone marrow (BM) fat resulting from adipocyte accumulation. Marrow adipocytes are active BM residents that influence the microenvironment by releasing cytokines, adipokines, and free fatty acids (FA). We explored the impact of palmitate (Palm) and oleate on function and survival of BM-derived mesenchymal stromal cells (MSC) of osteonecrotic patients (ONMSC) and healthy volunteers. Moreover, we analyzed the FA profile of the serum and the BM supernatant fluid (BMSF). We demonstrated that exposure to the saturated FA Palm favored MSC differentiation through the adipogenic lineage at the expense of the osteoblastic phenotype. Moreover, adipogenesis was intensified in ONMSC. The susceptibility to Palm toxicity was aggravated in ONMSC concomitantly with a greater activation of the proapoptotic extracellular signal-regulated kinase pathway. Moreover, cellular mechanisms implicated in the protection against lipotoxicity, such as stearoyl-coenzyme A desaturase 1 and carnitine palmitoyl transferase 1 expression, were dysregulated in ONMSC. Palm-induced interleukin (IL)-6 and IL-8 secretion was also exacerbated in ONMSC. Our results established that, in the serum, the FA profiles were comparable in ON and healthy subjects. However, both the concentrations and the FA composition were modified in the BMSF of ON patients, highlighting a drastic change of the BM microenvironment in ON patients. Altogether, our work suggests that marrow adipocyte enlargement could affect the process of bone remodeling and, therefore, play a role in the pathogenesis of ON.

D-glucose­ and 3-O-methyl-D-glucose-induced upregulation of selected genes in rat hepatocytes and INS1E cells: re­evaluation of the possible role of hexose phosphorylation.

The biochemical events involved in the upregulation of selected glucose­responsive genes by 3­O­methyl­D­glucose (3­MG) remain to be elucidated. The present study mainly aimed to re­evaluate the possible role of 3­MG phosphorylation in the upregulation of the thioredoxin interacting protein (TXNIP) and liver pyruvate kinase (LPK) genes in rat hepatocytes and INS1E cells. TXNIP and LPK transcription was assessed in rat liver and INS1E cells exposed to a rise in D­glucose concentration, 2­deoxy­D­glucose (2­DG), 3­MG and, when required, D­mannoheptulose. The phosphorylation of D­[U­14C]glucose and 3­O­[14C]methyl­D­glucose (14C-labeled 3-MG) was measured in rat liver, INS1E cell and rat pancreatic islet homogenates. The utilization of D­[5­3H]glucose by intact INS1E cells was also measured. In rat hepatocytes, a rise in the D­glucose concentration increased the TXNIP/hypoxanthine­guanine phosphoribosyl transferase (HPRT) and LPK/HPRT ratios, while 2­DG and 3­MG also increased the TXNIP/HPRT ratio, but not the LPK/HPRT ratio. In INS1E cells, the TXNIP/HPRT and LPK/HPRT ratios were increased in response to the addition of D­glucose, 2­DG and 3­MG. Furthermore, D­mannoheptulose abolished the response to D­glucose and 2­DG, but not to 3­MG, in these cells. Liver cell homogenates catalyzed the phosphorylation of 3­MG to a modest extent, whilst INS1E and rat pancreatic islet cell homogenates did not. Moreover, 3­MG marginally decreased D­glucose phosphorylation in INS1E cell homogenates but not in liver cell homogenates. D­[5­3H]glucose utilization by intact INS1E cells was decreased by 2­DG, but not by 3­MG. These findings reinforce the view that the upregulation of the TXNIP and LPK genes induced by 3­MG is not attributable to its phosphorylation or any favorable effect on D­glucose metabolism.

Immunocytochemistry of GLUT2, uptake of fluorescent desnitroso-streptozotocin analogs and phosphorylation of D-glucose in INS-1E cells.

The non-invasive imaging of GLUT2-expressing cells remains a challenge. As streptozotocin, and similarly alloxan, may be transported into cells by GLUT2, the major aim of the present study was to assess the possible use of fluorescent desnitroso-streptozotocin analogs for in vitro labeling of GLUT2-expressing cells. INS-1E cells, human embryonic kidney (HEK) cells, rat isolated pancreatic islets, rat hepatic cells, rat exocrine pancreatic cells and tumoral insulin-producing BRIN-BD11 cells were incubated in the presence of two distinct fluorescent desnitroso-streptozotocin analogs, probes A and B. The immunocytochemistry of GLUT2 in INS-1E cells and the phosphorylation of D-glucose by INS-1E cell homogenates were also examined. The uptake of probes A and B (12.0 µM) by INS-1E cells yielded apparent intracellular concentrations approximately one order of magnitude higher than the extracellular concentration. The two probes differed from one another by the absolute values for their respective uptake and time course, but not so by the pattern of their concentration dependency. Comparable results were recorded in HEK cells, rat isolated pancreatic islets and hepatocytes. Vastly different findings were recorded, however, in rat exocrine pancreatic cells, which do not express GLUT2. Moreover, an unusual concentration dependency for the uptake of each probe was observed in tumoral BRIN-BD11 cells. It is proposed that suitable fluorescent desnitroso-streptozotocin analogs may be used to label GLUT2-expressing cells.