Alendronate preserves femoral head shape and height/length ratios in an experimental rat model: A computer-assisted analysis.

BACKGROUND: Surgical osteonecrosis of the rat femoral head was induced by detaching the ligamentum teres and stripping the femoral neck periosteum. Bone and marrow necrosis were found from the fifth postoperative day and replaced by creeping substitution. Osteonecrosis of the femoral head results in the flattening to various degrees of roundness and osteoarthritic changes of the hip joint. Alendronate, an osteoclast inhibitor, slows down bone resorption and remodeling. The purpose of this study was to evaluate objectively the influence of alendronate treatment on the rat femoral head shape after six weeks of daily treatment, when compared with controls. MATERIALS AND METHODS: The blood circulation of right femoral head of 20 female Sprague-Dawley rats was interrupted. Twelve were treated by alendronate injections of 200 microg/kg/day and eight controls were treated with saline, both for a total of 42 days. Both femoral head specimens were obtained for computed-assisted morphometry. For each rat, the right operated head was compared with the left, and the alendronate treated group was compared with the control group. RESULTS: No differences were found in shape factor and femoral head height/length ratios in the alendronate treated femoral heads. Among the nontreated control group, shape-factor differences were found between the operated and the nonoperated femoral heads. CONCLUSION: Alendronate treatment prevented the distortion and destruction of the femoral head. Osteoclast inhibition might prolong the bone creeping substitution process and could enable secondary bone maturity and mineralization that increases bone strength. Alendronate preserved the femoral head architecture, which might reduce morbidity and disability due to femoral head collapse.

Patients aged 80 and older undergoing orthopedic or urologic surgery: a prospective study focusing on perioperative morbidity and mortality.

BACKGROUND: The population is progressively aging and an increasing number of elderly patients face surgical treatment. OBJECTIVE: The current study was designed to examine the perioperative morbidity and mortality of elderly patients undergoing orthopedic or urologic surgery and look for predictors for adverse outcome. METHODS: This is a prospective study of elderly patients, 80 years of age and older, who underwent elective or emergent orthopedic or urologic surgery in our institution during a 5-month period. Data were collected on age, gender, chronic diseases, number of regular medications, whether or not the patient was bedridden before surgery, American Society of Anesthesiologists (ASA) class, type of surgery and anesthesia, duration of hospitalization, and 30-day postoperative morbidity and mortality. We studied correlations between pre- and intraoperative parameters and postoperative complications. RESULTS: During the study period, 39 patients underwent urologic surgery and 147 patients underwent orthopedic surgery. Age ranged from 80 to 98 years (85 +/- 4.2 years, mean +/- SD). One patient had an intraoperative complication, 5 patients had postoperative complications within 1 day of surgery, and 23 had complications within 1 month of surgery. Five (2.7%) patients, all of whom were operated urgently, died after surgery. Postoperative complications correlated significantly to poor ASA class (p = 0.01), urgency of the procedure (p = 0.03), and extent (p = 0.02) and duration (p = 0.01) of surgery. No significant correlation was found between outcome and any other pre- or intraoperative factors. CONCLUSIONS: Elderly surgical patients with poor ASA class or following urgent, extensive or long surgery are at a higher risk for postoperative morbidity and mortality, mandating special perioperative care.

Low patient compliance--a major negative factor in achieving vitamin D adequacy in elderly hip fracture patients supplemented with 800IU of vitamin D3 daily.

Achievement of adequate vitamin D3 level is crucial for the treatment of hip fracture patients. Currently used vitamin D3 supplementation in Israel ranges between 200 and 800IU/day. The study objectives were to evaluate the effects of 800IU/day vitamin D3 and 1.200mg of calcium carbonate supplementation to achieve adequate vitamin D3 level of 30ng/ml in elderly hip fracture patients. One hundred and twenty-two elderly patients after surgical hip fracture correction aged 73.0+/-9.5, who were enrolled in a post-surgical treatment program (PSTP). The patients received 800IU of vitamin D3 and 1.200mg of calcium carbonate daily. Serum 25(OH)D and plasma PTH levels were assessed during initial hospital stay and at quarterly follow-up visits for 2 years. At baseline, 120 patients (98.4%) had 25(OH)D serum level <30ng/ml. Forty-two patients (34.4%) had 25(OH)D serum level <10ng/ml and these were considered as vitamin D(3) deficient. After 3 months, 29 patients (23.8%) were fully adherent to the supplement, 32 were (26.2%) partially adherent. The dropout rate at 1 year was 55.7%. The major reason for the discontinuation of participation was non-compliance. We conclude that the majority of elderly hip fracture patients had inadequate 25(OH)D serum levels. Compliance with calcium and vitamin D3 supplements was extremely low. An adequate vitamin D status was not achieved with daily vitamin D3 supplementation of 800IU. Supplementation strategies using a periodic single high dose of vitamin D3 might be more appropriate and should be considered in these patients.

Prevention of distortion of vascular deprivation-induced osteonecrosis of the rat femoral head by treatment with alendronate.

INTRODUCTION: In animals with a disrupted blood supply and drainage of the femoral head, the dead epiphyseal bone undergoes osteoclastic osteolysis and is replaced by newly synthesized, immature, and weak bone, which cannot withstand the daily loads and, therefore, the articular surface caves in. METHODS: Female Sprague-Dawley rats with interrupted blood circulation of the femoral head were treated with alendronate and compared to controls. RESULTS: There was no distortion of the femoral heads in the alendronate-treated animals. INTERPRETATION: Alendronate medication interferes with osteoclastic activities, slowing down bone turnover. These observations verify our hypothesis that osteoclastic activity is detrimental to the conservation of a hemispherical femoral head because of the rapidly occurring replacement of the dead by living tissues. Hence, halting the activities of the osteoclasts by alendronate stops the hasty new bone formation which is responsible for early femoral capital disfigurement.

Hip fractures in the elderly in Israel-possible impact of preventable conditions.

In the present study we evaluated the possible contribution of different factors to the occurrence of hip fractures in Israel. We assessed medical history, physical activity, body mass index, smoking status, bone turnover markers and calcium regulating hormones levels of 142 consecutive elderly hip fracture patients (HFP), and compared them to 96 community dwelling elderly people without a history of hip fracture. Age and female gender were the strongest predictors of hip fracture, p<0.001 and 0.013. Stepwise logistic regression demonstrated that HFP had higher PTH and lower 25(OH)D(3) levels, p=0.002, p<0.001; they were less physically active, p<0.001, and had higher rate of vitamin D insufficiency during winter-spring, compared to summer-autumn, p=0.033. Diabetics had higher risk for hip fracture, p=0.06, OR=3.9 (95% CI 1.50-10.4). Deoxypyridinoline (DPD) cross links levels were 19.35+/-10.58mg/mg creatinine in HFP and 9.12+/-3.52 in controls, p<0.0001. Bone alkaline phosphatase (BAP)/DPD ratio was 1.5 in controls compared to 0.53 in HFP. We conclude that age and female gender were the strongest predictors for hip fracture. Diabetic patients had threefold risk for hip fracture. Bone formation/bone resorption ratio was lower in HFP. Vitamin D deficiency and physical inactivity are important preventable risk factors for hip fracture.

Current criteria for hip fracture risk assessment--are we missing something?

BACKGROUND: Hip fracture rates are increasing worldwide, and the risk for a second hip fracture is high. The decision to administer antiresorptive treatment is based mainly on bone mineral density and/or a history of previous osteoporotic fractures. OBJECTIVES: To evaluate the contribution of BMD, previous fractures, clinical and laboratory parameters to hip fracture risk assessment. METHODS: The study population included 113 consecutive hip fracture patients, aged 72.5 +/- 9.4 years, discharged from the orthopedic surgery department. BMD was assessed at the lumbar spine, femoral neck and total hip. The results were expressed in standard deviation scores as T-scores--compared to young adults and Z-scores--compared to age-matched controls. Plasma or serum levels of parathyroid hormone, 25-hydroxyvitamin 3 and urinary deoxypyridinoline cross-links were evaluated. RESULTS: We observed T-scores < or = 2.5 in 43 patients (45.3%) at the lumbar spine, in 47 (52.2%) at the femoral neck and in 33 (38%) at the total hip. Twenty-eight patients (29.5%) had neither low BMD nor previous osteoporotic fractures. Using a T-score cutoff point of (-1.5) at any measurement site would put 25 (89%) of these patients into the high fracture risk group. Mean DPD level was 15.9 +/- 5.8 ng/mg (normal 4-7.3 ng/mg creatinine). Vitamin D inadequacy was observed in 99% of patients. CONCLUSIONS: Using current criteria, about one-third of elderly hip fracture patients might not have been diagnosed as being at risk. Lowering the BMD cutoff point for patients with additional risk factors may improve risk prediction yield.

A novel poly(ethylene glycol)-fibrinogen hydrogel for tibial segmental defect repair in a rat model.

The aim of this study is to investigate regeneration in a segmental bone defect using a novel fibrinogen-based hydrogel material. The use of hydrogels made from poly(ethylene glycol) (PEG) conjugated to fibrinogen for this purpose may be better to conventional fibrin-based materials as it offers an additional degree of control over the structural characteristics and biodegradation of the material. At the same time, it maintains some of the inherent biofunctionality of the fibrinogen molecule. PEGylated fibrinogen hydrogels with various degrees of proteolytic resistance based on PEG and fibrinogen composition were designed for slow, intermediate, and fast biodegradation. The hydrogels were implanted into 7-mm segmental rat tibial defects without additional osteoinductive factors with the rationale that the ingrowth matrix will displace the normal fibrin clot while sustaining a similar healing effect for a longer duration. Histological and X-ray results confirmed that the extent and distribution of newly formed bone in the defect after 5 weeks strongly parallels the biodegradation pattern of the implanted material. When compared to nonunions in animals treated with the fast-degrading implants and untreated control animals, the rats implanted with the intermediate-degrading material exhibited osteoneogenesis. This data supports the hypothesis that the perseverance of the PEGylated fibrinogen material can be synchronized with the optimal healing characteristics of a segmental osseous defect and that the consequent sustained release of fibrinogen fragments facilitates the osteogenic response at the injury site. The PEGylated fibrinogen material may, therefore, be a highly efficacious material for promoting the healing of bone defects and especially nonunion fractures.

Vasculature deprivation-induced osteonecrosis of rats' femoral heads associated with the formation of deep surface depressions.

BACKGROUND: Shallow or deep bowl-shaped depressions often develop after drilling an intraosseous conduit in the necrotic, avascular femoral head of rats. The etiopathogenesis of tissue loss at the articulation surface after a drilling procedure was elaborated in the authors' previous reports. GOALS: To scrutinize a large collection of femoral heads of rats in order to search for similar changes in cases in which no drilling procedure was carried out. STUDY: This retrospective study comprised the specimens of 386 rats with vessels-deprived osteonecrosis of the femoral heads, none of the animals having undergone a drilling procedure. RESULTS: Shallow or deep bowl-shaped depressions were encountered at an incidence as low as 2.8% of the femoral heads of the above mentioned 386 rats. It is not feasible to distinguish histologically the "spontaneously" arising from and drilling-related depressions. CONCLUSIONS: No assured explanation can be offered for the evolving depressions of the surface of femoral heads of rats, which have not undergone a drilling procedure. It is hypothesized that the synovial fluid forces its way via slits in the articulation surface and bores cavities in the substance of femoral heads, which display a postosteonecrotic osteoarthritis-like disorder. The rising pressure in the arthritic joints results, firstly, in an enlargement of these cavities and, secondly, loss of fibro-cartilaginous tissue such that the cavities come to communicate with the articular space.

Early administration of oral morphine to orthopedic patients after surgery.

Current pain treatment guidelines advise against providing analgesics for postoperative pain using intramuscular injections, as this generally provides poor pain relief. However, this route remains the most prevalent treatment method. Intravenous or epidural patient-controlled-analgesia methods reduce pain effectively but are expensive, labor intensive, and available to only a limited number of patients. We propose administering the analgesics using oral analgesics and have developed a simple protocol for treating postoperative pain by use of oral morphine. After a variety of orthopedic surgeries, patients were given "around-the-clock," oral, immediate-release morphine. Efficacy of the treatment (pain scores and adverse effects) was assessed 24 +/- 2 hours after surgery. Data were collected prospectively from 95 patients, who received an average of 61 +/- 30 (SD) mg morphine. Average pain scores were 2.4/10 (+/- 1.4) at rest and 4.0/10 (+/- 1.4) during movement in bed. Nausea and vomiting, the most common adverse effects, were reported by 22 (23 percent) patients. Naloxone was not administered to any of the patients. Oral morphine given in the early postoperative time to patients after a variety of orthopedic surgeries was effective and safe.

Arthroscopic subacromial decompression performed under local anesthesia.

Shoulder arthroscopy is usually performed under general anesthesia or interscalene block. General anesthesia may be contraindicated and interscalene block sometimes fails. We had 8 patients who were at high-risk and, therefore, shoulder arthroscopy and decompression were performed under local anesthesia in the beach-chair position. We used 50 mL of 1% lidocaine; 30 mL were infiltrated into the skin and underlying tissues and into the glenohumeral joint, and the rest was infiltrated into the subacromial joint. Before the infiltration, all patients were given 5 mg midazolam and 0.1 mg fentanyl intravenously. All 8 patients were satisfied with the analgesia provided by the anesthesia. We conclude that arthroscopy and subacromial decompression can be readily performed under local anesthesia in combination with efficient sedation.

Pyogenic granuloma-like reaction in the necrotic, vessels-deprived femoral head of the rat.

Osteonecrosis of the femoral head was produced in rats by cutting the ligamentum teres and incising the cervical periosteum. As of the second postoperative week, fibrous tissue pervaded the necrotic epiphyses, macrophages and osteoclasts removed the debris, osteoblasts deposited lamellar-fibred and woven-fibred intramembranous bone, and remodeling began. In 16% of the rats killed during the 2nd postoperative week, the epiphyses contained big fragments of necrotic bone enclosed by densely packed, capillary-sized vessels. Ingrowth of this hypervascularized, pyogenic granuloma-like tissue is presumably due to the presence of excessive growth factors, reflecting an exaggerated pathophysiological reaction within the framework of organization of the necrotic epiphyses.

The effects of enoxaparin on the reparative processes in experimental osteonecrosis of the femoral head of the rat.

The blood supply of one femoral head of 6-month-old rats was severed by incising the periosteum of the neck and cutting the ligamentum teres. The rats were killed on the 30th postoperative day and the femoral bones were obtained for semiquantification of the reparative processes in the necrotic heads. Fourteen rats were treated with enoxaparin and 14 untreated animals served as controls. Statistically, the amounts of necrotic bone in the epiphysis were less, the extent of remodeling of the femoral heads was milder, and the articular cartilage degeneration was slighter in the enoxaparin-treated than untreated rats. There was no significant difference in the quantities of newly formed bone in femoral heads of treated and untreated rats. These findings are in agreement with the known effects of unfractionated and low-molecular-weight heparins which enhance osteoclastic bone resorption and angiogenesis and decrease osteoblastic bone formation. The former activities, operative in minimizing the structural distortion of the femoral head, oppose the crucial event in the pathogenesis of post-osteonecrotic osteoarthritis.