Sensitivity and specificity of radiographic characteristics in atypical femoral fractures.

Using the American Society for Bone and Mineral Research Task Force case definition for atypical femoral fractures, sensitivity and specificity of radiographic fracture characteristics were calculated. Fracture pattern was the most sensitive and specific characteristic. This suggests that some characteristics should be weighted more heavily when identifying these fractures. INTRODUCTION: To estimate the sensitivity and specificity of each radiographic criterion in the 2013 ASBMR atypical femoral fracture (AFF) case definition for distinguishing AFF from other subtrochanteric/diaphyseal fractures (non-AFF) among women enrolled in a large integrated health care organization. METHODS: Radiographs from 55 physician-confirmed AFFs and a sample of 39 non-AFFs were reviewed by four independent expert reviewers representing four medical specialties. One image per fracture was selected for review. Using a standardized data collection tool, based on the 2013 AFF case definition, reviewers indicated the presence or absence of the following characteristics viewable on radiograph: fracture pattern, comminution, periosteal and/or endosteal thickening, and cortical thickening. Sensitivity and specificity for each characteristic was calculated for each reviewer and summarized across reviewers with the mean and range. Agreement across reviewers was quantified using Fleiss's kappa (FK) statistic. RESULTS: The most sensitive factors distinguishing AFF from non-AFF were lateral cortex transverse fracture pattern (mean 93.6 %, range 85.5-98.2 %), medial cortex transverse or oblique fracture pattern (mean 84.1 %, range 72.7-98.2 %), and minimal/non-comminution (mean 93.2 %, range 89.1-98.2 %). Specificity was the greatest for lateral cortex transverse fracture pattern (mean 95.5 %, range 92.3-97.4 %). Agreement across reviewers was the highest for lateral cortex transverse fracture pattern (FK 0.83) and incomplete fracture through the lateral cortex only (FK 0.80). CONCLUSION: Lateral cortex transverse fracture pattern was the most sensitive and specific characteristic and the most highly agreed upon across reviewers. Other characteristics were less readily agreed upon across reviewers. Measurement of discrete combinations of individual characteristics may enhance sensitivity and/or specificity.

Synergistic effects of HBO and PRP improve bone regeneration with autologous bone grafting.

Bone defects remain a challenge for patients and orthopaedic surgeons. Autologous transfer of cancellous bone grafts remains the standard of care. However, in recent years various osteoinductive substitute materials, such as platelet rich plasma (PRP) and hyperbaric oxygen therapy (HBO) have been shown to improve bone healing. This study evaluates the effects of a combined application of PRP and HBO with autologous bone grafting in an animal model. In 48 New Zealand White rabbits bone defects at the radius were filled with autologous bone harvested at the iliac crest. This was combined with application of autologous PRP and/or HBO treatment for the duration of this study. After 3 and 6 weeks histomorphometric, immunohistochemical and radiologic evaluations were performed. All animals tolerated the treatment well. Improved bone regeneration was shown in all groups at 6 weeks compared to 3 weeks. Additional application of PRP and HBO resulted in an increase in new bone formation and increased neovascularization at 3 and 6 weeks. There was no statistical significant difference between PRP and HBO application in these regards. A combinatory use of PRP and HBO resulted in an increased bone regeneration and neovascularization compared to all other groups. This study provides evidence for an improvement of bone regeneration with the combinatory application of PRP and HBO to autologous cancellous bone grafts in a model of weight bearing bone defects in rabbits. Also synergistic effects of these two measures on angiogenesis were evident.

Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model.

Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2µg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture.

Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects.

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non-union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty-four New-Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed.

Local insulin therapy affects fracture healing in a rat model.

A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.

Effects of PTH treatment on tibial bone of ovariectomized rats assessed by in vivo micro-CT.

UNLABELLED: Using in vivo microcomputed tomography (micro-CT), we found in parathyroid hormone (PTH)-treated osteopenic rats linear increases in cortical and trabecular, due to increased trabecular thickness and number, bone mass. Bone was formed in cavities, leading to restoral of nearly cleaved trabeculae. For the first time, effects in PTH-treated rats were analyzed longitudinally. INTRODUCTION: Our aims were to over time (1) determine changes in trabecular thickness and number after PTH, (2) compare responses to PTH between the meta- and epiphysis, (3) determine effects of PTH on mineralization and mechanical properties, (4) determine locations of new bone formation due to PTH on a microlevel, and (5) determine the predictive value of bone structural properties for gain in bone mass after PTH. METHODS: Adult rats were divided into ovariectomy (OVX; n = 8), SHAM-OVX (n = 8), and OVX and PTH treatment (n = 9). Between weeks 8 and 14, PTH rats received daily subcutaneous PTH injections (60 microg/kg/day). At weeks 0, 8, 10, 12, and 14, in vivo micro-CT scans were made of the proximal and diaphyseal tibia. After sacrifice, all tibiae were tested in three-point bending. RESULTS: PTH increased bone volume fraction linearly over time in meta- and epiphysis, accompanied by increased trabecular thickness in both and increased trabecular number only in the latter one. CT-estimated mineralization increased in trabecular and remained constant in cortical bone. Ultimate load and energy were increased and ultimate displacement and stiffness unaltered compared to SHAM rats. For those trabeculae analyzed, bone was formed initially on places where it was most beneficial for increasing their strength and later on to all surfaces.

Beneficial effect of zinc supplementation on biomechanical properties of femoral distal end and femoral diaphysis of male rats chronically exposed to cadmium.

The present study was aimed at estimate, based on the rat model of human moderate and relatively high chronic exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced weakening in the bone biomechanical properties. For this purpose, male Wistar rats were administered Cd (5 or 50 mg/l) or/and Zn (30 or 60 mg/l) in drinking water for 6 and 12 months. Bone mineral density (BMD) and biomechanical properties (yield load, ultimate load, post-yield load, displacement at yield and at ultimate, stiffness, work to fracture, yield stress, ultimate stress and Young modulus of elasticity) of the femoral distal end and femoral diaphysis were examined. Biomechanical properties of the distal femur were estimated in a compression test, whereas those of the femoral diaphysis -- in a three-point bending test. Exposure to Cd, in a dose and duration dependent manner, decreased the BMD and weakened the biomechanical properties of the femur at its distal end and diaphysis. Zn supplementation during Cd exposure partly, but importantly, prevented the weakening in the bone biomechanical properties. The favorable Zn influence seemed to result from an independent action of this bioelement and its interaction with Cd. However, Zn supply at the exposure to Cd had no statistically significant influence on the BMD at the distal end and diaphysis of the femur. The results of the present paper suggest that Zn supplementation during exposure to Cd may have a protective influence on the bone tissue biomechanical properties, and in this way it can, at least partly, decrease the risk of bone fractures. The findings seem to indicate that enhanced dietary Zn intake may be beneficial for the skeleton in subjects chronically exposed to Cd.

Trauma-induced changes in diaphyseal cross-sectional geometry in two elites from Copan, Honduras.

This research utilized biplanar radiographs to estimate cross-sectional biomechanical properties for the skeletal remains of two elite individuals from the Early Classic period (ca. AD 400-600) of Copan, Honduras: K'inich Yax K'uk' Mo' (Hunal Burial 95-2), founder of the Early Classic Dynasty at Copan, and the primary female interment (Burial 37-8) from the Motmot tomb. Both individuals survived severe blunt-force insults to the right forearm. Gross skeletal examination and evaluation of the radiographs for K'inich Yax K'uk' Mo' suggest that these traumas resulted from, at least in part, disuse atrophy of the affected forearm skeletal elements. Gross and radiologic evaluation of the Motmot remains countered the possibility that she suffered from a metabolic bone disease, and confirmed the presence of a well-healed parry fracture of the right ulna. The degree of asymmetry in cross-sectional biomechanical properties reported here for K'inich Yax K'uk' Mo' is likely the secondary result of the described blunt-force trauma. The results obtained for the principal Motmot interment are not as dramatic, but suggest subtle changes to humeral cross-sectional geometry subsequent to trauma.

Musculoskeletal analyses of the forearm in young women with Turner syndrome: a study using peripheral quantitative computed tomography.

Turner syndrome (TS) is associated with multiple skeletal abnormalities. Fracture incidence appears to be increased, but the reasons for this are not entirely clear. In the present study, we used peripheral quantitative computed tomography to evaluate bone mass, density, geometry, and strength of the radial metaphysis and diaphysis as well as maximum forearm muscle cross-sectional area (CSA) in a group of 21 TS patients. These individuals were 19.5 +/- 2.3 yr of age (mean +/- SD; range, 16.2-25.4 yr) and had completed growth after having received GH therapy; all but one were receiving estrogen supplementation. Despite short stature, cross-sectional bone size was normal compared with age-matched healthy controls. However, bone mineral content was decreased, resulting in a low total volumetric bone mineral density. This was due to decreased cortical thickness at both sites of measurement, whereas trabecular volumetric bone mineral density of the metaphysis was normal. Muscular CSA was normal. The relationship between muscle CSA and external bone size was similar between TS patients and healthy young women. However, TS patients had less bone mineral content and cortical CSA relative to muscle CSA than healthy young women, but similar muscle-bone relationships as healthy prepubertal girls. These findings are compatible with a normal adaptation of external bone size to the mechanical loads imposed by the muscle system and a lack of pubertal effect on the endocortical bone surface, despite estrogen supplementation. Bone strength may not be adequate for the relatively high body weight of TS patients (+0.8 SD score), which could contribute to an increased propensity for fractures.

Long-term effects of intravenous 1 alpha (OH)D3 combined with CaCO3 and low-calcium dialysis on secondary hyperparathyroidism and biochemical bone markers in patients on chronic hemodialysis.

The effects of intravenous administration of 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3] in combination with CaCO3 and 'low-calcium dialysis' (1.25 mmol/l) on plasma (p) parathyroid hormone (PTH) and biochemical bone markers (osteocalcin, alkaline phosphatase, procollagen type 1 c-terminal extension peptide) were examined in 54 patients on chronic hemodialysis with either normal or elevated PTH. Increasing doses of 1 alpha (OH)D3 were administered intravenously under careful control of p-Ca2+ and inorganic phosphate. Blood samples were obtained 1 week before the start of treatment and then every 2nd week. 20 patients with initially normal PTH levels (23.5 +/- 4.17 pg/ml) and 34 patients with initially elevated PTH levels (301 +/- 45 pg/ml) were followed for up to 88 weeks. The present investigation: demonstrated: (1) 'Low-calcium hemodialysis' (1.25 mmol/l) made it possible to use larger doses of CaCO3 and to reduce the doses of an aluminium-containing oral phosphate binder. A decrease in p-Ca2+ during dialysis was induced, and special care had to focus on the compliance to CaCO3, in order not to aggravate the secondary hyperparathyroidism. (2) The combination of 'low-calcium hemodialysis', CaCO3, and pulse intravenous 1 alpha (OH)D3 prevented the development of secondary hyperparathyroidism in patients with normal PTH levels and induced a long-term suppression of p-PTH (106 +/- 25 pg/ml, 88 weeks) in the patients with secondary hyperparathyroidism. By careful monitoring, severe hypercalcemia and hyperphosphatemia were avoided. There were no indications, clinically or biochemically, of development of adynamic bone disease. (3) Bone lesions were healed and a decrease of the bone mineral content in lumbar spine and femoral neck of patients with both normal and elevated PTH levels prevented. (4) The present results may suggest that PTH might be of influence on that regulation of procollagen type 1 c-terminal extension peptide.