No abstract

The purpose of this study was to examine the complications and outcomes of total hip replacement (THR) in super-obese patients (body mass index (BMI) > 50 kg/m(2)) compared with class I obese (BMI 30 to 34.9 kg/m(2)) and normal-weight patients (BMI 18.5 to 24.9 kg/m(2)), as defined by the World Health Organization. A total of 39 THRs were performed in 30 super-obese patients with a mean age of 53 years (31 to 72), who were followed for a mean of 4.2 years (2.0 to 11.7). This group was matched with two cohorts of normal-weight and class I obese patients, each comprising 39 THRs in 39 patients. Statistical analysis was performed to determine differences among these groups with respect to complications and satisfaction based on the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index, the Harris hip score (HHS) and the Short-Form (SF)-12 questionnaire. Super-obese patients experienced significantly longer hospital stays and higher rates of major complications and readmissions than normal-weight and class I obese patients. Although super-obese patients demonstrated reduced pre-operative and post-operative satisfaction scores, there was no significant difference in improvement, or change in the score, with respect to HHS or the WOMAC osteoarthritis index. Super-obese patients obtain similar satisfaction outcomes as class I obese and normal-weight patients with respect to improvement in their scores. However, they experience a significant increase in length of hospital stay and major complication and readmission rates.

General outcome measures were favorable. Smokers and patients with workers' compensation claims experienced significantly poorer outcomes. However, the incidence of nonunion and delayed union was higher than most reports in the literature. Furthermore, we demonstrated a high refracture rate (11.4 %) following removal of hardware.

Using an animal model of heparin-induced osteoporosis we previously demonstrated that heparin causes bone loss, in part, by increasing osteoclast number and activity. Furthermore, we found that, although heparin alone has no effect, it is able to synergistically enhance Interleukin-11 (IL-11)-induced signal transducer and activator of transcription 3 (STAT3) activation and thus increase osteoclast formation in vitro. In the present study, we examine the effect of various serine kinase inhibitors on the ability of heparin to act synergistically with IL-11. Inhibition of the c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), or the phosphatidylinositol 3-kinase pathways had no effect on the ability of heparin to promote either IL-11-induced STAT3⅐DNA complex formation or osteoclast formation in vitro. In contrast, PD098059, a MAPK kinase inhibitor, completely abolished the synergy between heparin and IL-11. In an attempt to resolve the mechanism by which this was occurring, we examined the effect of heparin on STAT3 Ser-727 phosphorylation and extracellular signal-regulated kinases 1 and 2 (Erk1/2) activation, either in the presence or absence of IL-11. Heparin alone was found to have no effect on Ser-727 phosphorylation, nor did heparin alter the phosphorylation status of Ser-727 in the presence of IL-11. Heparin was, however, found to increase Erk1/2 activation in both a time-and dose-dependent manner. When taken together, these findings suggest that heparin enhances IL-11-induced STAT3 activation and thus osteoclast formation, by a mechanism that is independent of STAT3 Ser-727 phosphorylation but that involves up-regulation of the MAPK pathway.Osteoporosis is a well recognized complication of long term heparin therapy (1-9). However, little is known about the mechanism by which heparin causes bone loss. To address this issue we developed several in vitro and in vivo models with which to study the effects of heparin on bone. By using these models, we showed that heparin causes both a time-and a dosedependent decrease in cancellous bone and that this, in part, results from an increase in osteoclast number and activity (10 -12). In addition, we found that heparin alone has no effect on osteoclast formation, but rather it acts synergistically with interleukin-11 (IL-11), 3 a member of the IL-6 family of cytokines, to enhance both IL-11 signaling and in vitro osteoclast formation (13). When taken together, these findings suggest that IL-11 plays a critical role in the ability of heparin to induce osteoclast formation. This finding may account for the increase in bone resorption that we observe in our animal models of heparin-induced osteoporosis.IL-11 belongs to a family of cytokines that includes IL-6, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin-1 (14). All members of this family display multiple effects on both hematopoietic and nonhematopoietic cell populations, and as such, are known to stimulate osteoclast formation both in vitro and in vivo...