Background and purpose Immediate implant stability is a key factor for success in cementless total hip arthroplasty (THA). Low bone mineral density (BMD) and age-related geometric changes of the proximal femur may jeopardize initial stability and osseointegration. We compared migration of hydroxyapatite-coated femoral stems in women with or without low systemic BMD.Patients and methods 61 female patients with hip osteoarthritis were treated with cementless THA with anatomically designed hydroxyapatite-coated femoral stems and ceramic-ceramic bearing surfaces (ABG-II). Of the 39 eligible patients between the ages of 41 and 78 years, 12 had normal systemic BMD and 27 had osteopenia or osteoporosis. According to the Dorr classification, 21 had type A bone and 18 had type B. Translational and rotational migration of the stems was evaluated with radiostereometric analysis (RSA) up to 2 years after surgery.Results Patients with low systemic BMD showed higher subsidence of the femoral stem during the first 3 months after surgery than did those with normal BMD (difference = 0.6, 95% CI: 0.1–1.1; p = 0.03). Low systemic BMD (odds ratio (OR) = 0.1, CI: 0.006–1.0; p = 0.02), low local hip BMD (OR = 0.3, CI: 0.1–0.7; p = 0.005) and ageing (OR = 1.1, CI: 1.0–1.2; p = 0.02) were risk factors for delayed translational stability. Ageing and low canal flare index were risk factors for delayed rotational stabilization (OR = 3, CI: 1.1–9; p = 0.04 and OR = 1.1, CI: 1.0–1.2; p = 0.02, respectively). Harris hip score and WOMAC score were similar in patients with normal systemic BMD and low systemic BMD.Interpretation Low BMD, changes in intraosseous dimensions of the proximal femur, and ageing adversely affected initial stability and delayed osseointegration of cementless stems in women.

OBJECTIVE-A functional polymorphism leucine 7 proline in the human neuropeptide Y (NPY) gene leading to increased NPY release from sympathetic nerves is associated with traits of metabolic syndrome. Although hypothalamic NPY neurons play an established role in promoting positive energy balance, the role of NPY colocalized with norepinephrine in sympathetic nervous system and brain noradrenergic neurons remains obscure.RESEARCH DESIGN AND METHODS-To clarify the role of NPY in noradrenergic neurons, we generated a transgenic mouse overexpressing NPY under dopamine-␤-hydroxylase promoter and characterized the metabolic phenotype of the OE-NPY D␤H mouse.RESULTS-NPY levels are increased by 1.3-fold in adrenal glands and 1.8-fold in the brainstem but not in the hypothalamus in OE-NPY D␤H mice. They display increased white adipose tissue mass and cellularity and liver triglyceride accumulation without hyperphagia or increased body weight. Hyperinsulinemia and impaired glucose tolerance develop by the age of 6 months in the OE-NPY D␤H mice. Furthermore, circulating ghrelin is significantly increased in comparison with wild-type mice.CONCLUSIONS-The present study shows that even a moderate increase in NPY levels in noradrenergic neurons leads to disturbances in glucose and lipid metabolism. The OE-NPY D␤H mouse is an interesting new model to investigate the pathophysiology of some key components of the cluster of abnormalities characterizing the metabolic syndrome. Diabetes 57: [1517][1518][1519][1520][1521][1522][1523][1524][1525] 2008 N europeptide Y (NPY) plays a well-established role in the hypothalamic control of body energy balance. It is one of the key components of the interconnected orexigenic network, which is upregulated in states of negative energy balance. NPY is a very potent orexigenic peptide, and when chronically administered into the central nervous system, it leads to increased food intake, weight gain, and adiposity (1-3). NPY-induced obesity is not only due to hyperphagia; centrally administered NPY also promotes white adipose tissue (WAT) lipid storage, inhibits brown adipose tissue thermogenesis, and induces hyperinsulinemia and hypercorticosteronemia (4 -6). Increased hypothalamic NPY is also an essential feature of leptin-deficient obesity, which is attenuated by genetic depletion of NPY (7). Although there is plenty of evidence on the key role of NPY in the regulation of energy balance in rodents, the evidence is scarce in humans and based mainly on the functional leucine 7 proline (L7P) polymorphism of the preproNPY associated with alterations in glucose and lipid metabolism and development of atherosclerosis (8).In addition to the NPY neurons of the hypothalamus, NPY is widely distributed in the central and peripheral nervous system. In the periphery, NPY is co-stored and co-released in postganglionic sympathetic neurons and chromaffin cells of adrenal medulla with norepinephrine (NE) (9,10). In the brain, NPY is also colocalized with NE in noradrenergic neurons in the medulla and the brain...

Background and purpose Factors that lead to periprosthetic bone loss following total hip arthroplasty (THA) may not only depend on biomechanical implant-related factors, but also on various patient-related factors. We investigated the association between early changes in periprosthetic bone mineral density (BMD) and patient-related factors.Patients and methods 39 female patients underwent cementless THA (ABG II) with ceramic-ceramic bearing surfaces. Periprosthetic BMD in the proximal femur was determined with DXA after surgery and at 3, 6, 12, and 24 months. 27 patient-related factors were analyzed for their value in prediction of periprosthetic bone loss.Results Total periprosthetic BMD was temporarily reduced by 3.7% at 3 months (p < 0.001), by 3.8% at 6 months (p < 0.01), and by 2.6% at 12 months (p < 0.01), but recovered thereafter up to 24 months. Preoperative systemic osteopenia and osteoporosis, but not the local BMD of the operated hip, was predictive of bone loss in Gruen zone 7 (p = 0.04), which was the only region with a statistically significant decrease in BMD (23%, p < 0.001) at 24 months. Preoperative serum markers of bone turnover predicted the early temporary changes of periprosthetic BMD. The other patient-related factors failed to show any association with the periprosthetic BMD changes.Interpretation Female patients with low systemic BMD show greater bone loss in Gruen zone 7 after cementless THA than patients with normal BMD. Systemic DXA screening for osteoporosis in postmenopausal patients before THA could be used to identify patients in need of prophylactic anti-resorptive therapy.

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Background and purposeLow bone mineral density (BMD) may jeopardize the initial component stability and delay osseointegration of uncemented acetabular cups in total hip arthroplasty (THA). We measured the migration of uncemented cups in women with low or normal BMD.Patients and methodsWe used radiostereometric analysis (RSA) to measure the migration of hydroxyapatite-coated titanium alloy cups with alumina-on-alumina bearings in THA of 34 female patients with a median age of 64 (41–78) years. 10 patients had normal BMD and 24 patients had low systemic BMD (T-score ≤ −1) based on dual-energy X-ray absorptiometry (DXA). Cup migration was followed with RSA for 2 years. Radiographic follow-up was done at a median of 8 (2–10) years.ResultsPatients with normal BMD did not show a statistically significant cup migration after the settling period of 3 months, while patients with low BMD had a continuous proximal migration between 3 and 12 months (p = 0.03). These differences in cup migration persisted at 24 months. Based on the perceived risk of cup revision, 14 of the 24 cases were “at risk” (proximal translation of 0.2 to 1.0 mm) in the low-BMD group and 2 of the10 cases were “at risk” in the normal-BMD group (odds ratio (OR) = 8.0, 95% CI: 1.3–48). The radiographic follow-up showed no radiolucent lines or osteolysis. 2 cups have been revised for fractures of the ceramic bearings, but none for loosening.InterpretationLow BMD contributed to cup migration beyond the settling period of 3 months, but the migrating cups appeared to osseointegrate eventually.

Low bone quality may compromise the success of cementless total hip arthroplasty in high-risk patients such as elderly women. Zoledronic acid is a long-lasting antiresorptive agent, which is known to reduce short-term periprosthetic bone loss. However, its effect on femoral stem stability is not well known. Forty-nine female patients with a mean age of 68 years (range, 51-85 years) scheduled to undergo cementless total hip arthroplasty due to osteoarthritis were randomized in this double-blind, placebo-controlled trial to receive a single postoperative infusion of zoledronic acid or placebo. Patients were evaluated for up to four years postoperatively for femoral stem migration measured by radiostereometric analysis, bone mineral density (BMD) measured by dual X-ray absorptiometry, functional recovery, and patient-reported outcome scores. Implant survival was determined at nine years postoperatively. Zoledronic acid did not reduce the femoral stem migration that occurred predominantly during the settling period of the first 3-6 months. Subsequently, all femoral stems were radiographically osseointegrated. Zoledronic acid maintained periprosthetic BMD, while the expected loss of periprosthetic bone during the first 12 months was found in controls. Thereafter, periprosthetic BMD of Gruen zone 7 decreased even in the zoledronic acid group but remained 14.6% higher than that in the placebo group at four years postoperatively. Functional recovery was comparable across the groups. At nine years postoperatively, no revision arthroplasty had been performed. In conclusion, in women at high-risk for low BMD, zoledronic acid had a long-lasting, partially protective effect on periprosthetic bone loss, but the treatment did not enhance the initial femoral stem stability.

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One main application of resorbable poly-L-lactic acid (PLLA) and poly-L-lactic-co-glycolic acid (PLGA) based materials is in medical implants. In this study composites were made from PLLA and PLGA with hydroxyapatite (HAp) respective beta-tricalcium phosphate (beta-TCP) fillers. The filler content and particle size were varied, and the thermal properties as well as the mechanical strength of the composites were investigated. The composites were made by an extrusion compounding process giving 2-2.5 mm diameter sized profiles. The results verified that the thermal stability of the composites was reasonable during the optimized compounding conditions. Scanning electron microscopy revealed that the fillers were well dispersed in the polymer matrices. The mechanical properties were improved by the addition of the fillers. The optimum mechanical properties for the extruded profiles were obtained with the HAp fillers. The E-modulus was increased from 3.3 to 4.6 GPa by addition of filler particles (30 wt%) whereas the flexural strength was reduced from 133 to 106 MPa.