Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture

Remodeling imbalance in the elderly femoral neck can result in thin cortices and porosity predisposing to hip fracture. Hip osteoarthritis protects against intracapsular hip fracture. By secreting sclerostin, osteocytes may inhibit Wnt signaling and reduce bone formation by osteoblasts. We hypothesised that differences in osteocytic sclerostin expression might account for differences in osteonal bone‐formation activity between controls and subjects with hip fracture or hip osteoarthritis. Using specific antibody staining, we determined the osteocytic expression of sclerostin within osteons of the femoral neck cortex in bone removed from subjects undergoing surgery for hip osteoarthritis (hOA: 5 males, 5 females, 49 to 92 years of age) or hip fracture fixation (FNF: 5 males, 5 females, 73 to 87 years of age) and controls (C: 5 males, 6 females, 61 to 90 years of age). Sclerostin expression and distances of each osteocyte to the canal surface and cement line were assessed for all osteonal osteocytes in 636 unremodeled osteons chosen from fields (～0.5 mm in diameter) with at least one canal staining for alkaline phosphatase (ALP), a marker of bone formation. In adjacent sections, ALP staining was used to classify basic multicellular unit (BMUs) as quiescent or actively forming bone (ALP⁺). The areal densities of scl^? and scl⁺ osteocytes (number of cells per unit area) in the BMU were inversely correlated and were strong determinants of ALP status in the BMU. In controls and hip fracture patients only, sclerostin‐negative osteocytes were closer to osteonal surfaces than positively stained cells. Osteon maturity (progress to closure) was strongly associated with the proportion of osteonal osteocytes expressing sclerostin, and sclerostin expression was the chief determinant of ALP status. hOA patients had 18% fewer osteocytes per unit bone area than controls, fewer osteocytes expressed sclerostin on average than in controls, but wide variation was seen between subjects. Thus, in most hOA patients, there was increased osteonal ALP staining and reduced sclerostin staining of osteocytes. In FNF patients, newly forming osteons were similar in this respect to hOA osteons, but with closure, there was a much sharper reduction in ALP staining that was only partly accounted for by the increased proportions of osteonal osteocytes staining positive for sclerostin. There was no evidence for a greater effect on ALP expression by osteocytes near the osteonal canal. In line with data from blocking antibody experiments, osteonal sclerostin appears to be a strong determinant of whether osteoblasts actively produce bone. In hOA, reduced sclerostin expression likely mediates increased osteoblastic activity in the intracapsular cortex. In FNF, full osteonal closure is postponed, with increased porosity, in part because the proportion of osteocytes expressing sclerostin increases sharply with osteonal maturation. © 2010 American Society for Bone and Mineral Research     

Internal fixation of femoral neck fractures: a prospective study

To determine the adequacy of reduction and the soundness of the technique of primary internal fixation, the authors studied prospectively 96 femoral neck fractures over 6 1/2 years. Patients were followed up for an average of 11 months. The mean patient age was 70 years. Both clinical and radiologic data were collected at 3-month intervals for 6 months and then annually. Radiologic indices recorded included the Garden classification and index, shear angle, Western Infirmary Glasgow angle, lateral angle, nail placement, occurrence of bony union and presence of avascular necrosis. The fixation devices included sliding compression screw and side plate, multiple Knowles pins and a 130 degrees AO blade plate. A high rate of varus reduction, excessive ante- or retroversion and poor nail placement were all noted. Twenty-three patients required a total of 36 reoperations. There were six deaths in the first 6 months after operation. Eighty-five patients (mean age 79 years) with femoral neck fractures treated by hemiarthroplasty (71) or total hip replacement (14) during the same period were also reviewed. Follow-up averaged 8 months. Two patients required reoperation. The general morbidity was similar to that of the group treated by internal fixation, but there were eight deaths. Femoral neck fractures, if treated by internal fixation, demand accurate reduction and fixation for optimum results. Primary prosthetic replacement should be reserved for elderly patients with poor bone stock.     

脆性股骨颈骨折的股骨颈皮质厚度和骨密度改变

目的 研究脆性股骨颈骨折的股骨颈皮质骨厚度和骨密度变化。方法 对76例病人行股骨近端CT扫描,骨质疏松性股骨颈骨折组42 例,非骨折组34 例。取对侧（正常侧）股骨小转子顶点上方20mm（T20）平面CT横截面影像,计算T20长径和股骨颈寛径皮质比率,作为评估皮质厚度的指标;用DXA测量股骨颈骨密度,了解骨质疏松程度。结果 T20长径皮质比率：骨质疏松性股骨颈骨折组：（17.57±3.54）% ;非骨折组：（21.64±3.75）%（P =0.000）;T20股骨颈宽径皮质比率：骨质疏松性股骨颈骨折组：（25.98±5.51）%;非骨折组：(32.89±5.74)%（P=0.000）。骨密度：骨折组：0.590±0.084 g/cm2 ;非骨折组：0.698±0.138g/cm2, , P <0.000。结论 股骨颈皮质变薄和骨密度降低是导致脆性股骨颈骨折重要因素,T20长径皮质比率和T20股骨颈宽径皮质比率是观察股骨颈皮质骨变化的有效指标。     

Male-female differences in the association between incident hip fracture and proximal femoral strength: a finite element analysis study

Hip fracture risk is usually evaluated using dual energy X-ray absorptiometry (DXA) or quantitative computed tomography (QCT) which provide surrogate measures for proximal femoral strength. However, proximal femoral strength can best be estimated explicitly by combining QCT with finite element (FE) analysis. To evaluate this technique for predicting hip fracture in older men and women, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Baseline (pre-fracture) QCT scans of 5500 subjects were obtained. During 4-7 years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as age- and sex-matched controls. FE-strength of the left hip of each subject for stance (F(Stance)) and posterolateral fall (F(Fall)) loading, and total femur areal bone mineral density (aBMD) were computed from the QCT data. F(Stance) and F(Fall) in incident hip fracture subjects were 13%-25% less than in control subjects (p ≤ 0.006) after controlling for demographic parameters. The difference between FE strengths of fracture and control subjects was disproportionately greater in men (stance, 22%; fall, 25%) than in women (stance, 13%; fall, 18%) (p ≤ 0.033), considering that F(Stance) and F(Fall) in fracture subjects were greater in men than in women (p < 0.001). For men, F(Stance) was associated with hip fracture after accounting for aBMD (p = 0.013). These data indicate that F(Stance) provides information about fracture risk that is beyond that provided by aBMD (p = 0.013). These findings support further exploration of possible sex differences in the predictors of hip fracture and of sex-specific strategies for using FE analysis to manage osteoporosis.     

Osteocytic expression of constitutive NO synthase isoforms in the femoral neck cortex: a case-control study of intracapsular hip fracture.

NO is an osteocytic signaling molecule that can inhibit osteoclasts. The NO synthases eNOS and nNOS were expressed by >50% of osteonal osteocytes in controls. Hip fracture cases showed +NOS osteocytes only in deep osteonal bone, and 25-35% reduced expression overall. These data are consistent with increased osteonal vulnerability to deep osteoclastic attack. INTRODUCTION: Osteocytes may regulate the response to mechanical stimuli in bone through the production of local signaling molecules such as NO derived from the NO synthase eNOS. Because NO is inhibitory to osteoclastic resorption, it has been suggested that osteocytes expressing eNOS act as sentinels, confining resorption within single osteons. Recently, nNOS has been shown to be present in osteocytes of adult human bone. MATERIALS AND METHODS: Cross-sections of the femoral neck (eight female cases of intracapsular hip fracture and seven postmortem controls; age, 68-91 years) were analyzed by immunohistochemistry. The percentages of osteocytes expressing each of these two isoforms were calculated, and their distances to the nearest canal surface were measured. RESULTS: The percentage of +nNOS osteocytes was lower in the fracture cases than in the controls (cases: 43.12 +/- 1.49, controls: 56.68 +/- 1.45; p < 0.0001). Compared with nNOS, eNOS expression was further reduced (p = 0.009) in the cases but was not different in the controls (cases: 36.41 +/- 1.53, controls: 56.47 +/- 2.41; p < 0.0001). The minimum distance of +eNOS or +nNOS osteocytes to a canal surface was higher in the cases compared with controls (eNOS: controls; 44.4 +/- 2.2 microm, cases: 61.7 +/- 2.0 microm; p < 0.0001; nNOS: controls: 52.4 +/- 1.7 microm, cases: 60.2 +/- 2.1 microm; p = 0.0039). +eNOS osteocytes were closer to the canal surfaces than +nNOS osteocytes in the controls by 8.00 +/- 4.0 microm (p = 0.0012). CONCLUSION: The proportions of osteocytes expressing nNOS and eNOS were both reduced in the fracture cases, suggesting that the capacity to generate NO might be reduced. Furthermore, the reduction in NOS expression occurs in those osteocytes closest to the canal surface, suggesting that the ability of NO to minimize resorption depth might be impaired. Further studies are needed on the regulation of the expression and activity of these distinct NOS isoforms.     

The bone mineral content and cortical thickness in young women with femoral neck fracture

The bone mineral content in the shafts of the forearm in 17 women with cervical fracture of the upper end of the femur was low. The cortex of the femoral neck was also lower than normal. Thus women with hip fractures at an early age may have lower than average total skeletal tissue density. This may be due not simply to systemic osteoporosis but possibly to constitutionally thin bone cortices.     

陈旧性股骨颈骨折的全髋关节置换术

目的 探讨全髋关节置换术(total hip arthroplasty,THA)治疗陈旧性股骨颈骨折的假体选择与技术特点.方法 2001年10月至2006年11月因陈旧性股骨颈骨折接受THA患者60例,男30例,女30例;年龄30～80岁,平均57.5岁.按骨折后经保守治疗(23例)或内固定治疗(37例)分组.比较两组股骨柄使用类型、髓腔张开指数、骨质疏松程度.分析术前、术后肢体长度差、股骨头加长长度及旋转中心位置.结果 4l例获得随访,平均随访时间为18-4个月(2～48个月).(1)保守治疗与内固定治疗组骨水泥型柄使用率分别为61%、27%(P<0.05);术前患侧股骨髓腔张开指数分别为2.62±0.85、3.23±0.68(P<0.05);Barnett指数分别为0.40±0.15、0.48±0.08(P<0.05);股骨距平均长度为(0.9±0.6)cm;(2)53%的患者术前髋臼侧骨质疏松等级患侧大于健侧;术后Delce 1、2、3区出现透光线的患者分别占33%、15%及17%(P<0.05);(3)术前、术后平均肢体长度差分别为(21.8±13.0)mm、(1.5±6.7)mm,股骨头平均加长(5.4±2.2)mm.结论 经内崮定治疗后的患者骨质及形态优于经保守治疗者.内固定组股骨柄易被置于内翻位.陈旧性股骨颈骨折多伴有骨质疏松,易发生过度磨锉,导致髋臼安置上移.骨折后瘢痕组织弹性差,易过度松解而不得不使用加长股骨头颈,因此术中应注意软组织松解的程序和范围.     

Changes in total alkaline phosphatase level after hip fracture: comparison between femoral neck and trochanter fractures

Background Biochemical bone metabolic markers are affected by fractures, and total alkaline phosphatase (ALP) is considered one of the bone formation markers. Only a few reports have dealt with changes in bone formation markers during the healing process of bone fragility hip fractures. Despite the difference in the amount of callus formation and bone fusion rate, no significant differences in longitudinal change of total ALP between femoral neck and trochanter fracture have been reported. Methods A total of 69 osteoporotic patients with femoral neck or trochanter fracture whose serum concentrations of total ALP were examined at least four times at six periodic examination points (1, 2, 3, 4, 6, and 8 weeks after surgery) and whose state of bone union was obtained within 24 weeks after surgery were selected for this retrospective study. The characteristic longitudinal change of total ALP during the healing process was shown, and the possibility of total ALP as a predictive factor for the state of osteosynthesis of hip fractures is discussed. Results Changes in the total ALP level according to the healing process were similar for femoral neck and trochanter fractures. The concentration of total ALP rose to a maximum at 3 weeks after surgery and then gradually decreased for both fractures. However, the range of change was significantly greater for trochanter fractures than for femoral neck fractures. For trochanter fractures, total ALP decreased from 3 to 6 weeks after surgery in all but one patient. Conclusions Increases in the concentration of total ALP after surgery and the subsequent decreases may reflect the normal healing process. A significant difference in the changes of total ALP after surgery between femoral trochanter and neck fractures was shown. Periodic measurement of total ALP might be useful for obtaining information on the osteosynthesis state.     

Sliding of the compression hip screw in femoral neck fractures

Backing out of the compression screw in the sliding screw-plate hip osteosynthesis was analyzed in a series of 71 hips with medial femoral neck fractures during an observation period of 12-42 months, with a median of 26 months. In addition to the compression screw device, a parallel cranial lag screw was used. A postoperative primary diastasis in the fracture space of 1-5 mm in 11 cases did not predispose to major sliding of the screws or to healing problems. Thirteen of 27 fractures with late screw telescoping of 4 mm or more showed healing disturbances, 11 late segmental collapses, and 2 nonunions, compared with 7 disturbances, 6 late segmental collapses, and 1 nonunion among 39 cases with screw gliding of 3 mm or less. The difference was significant (p less than 0.05, Mann-Whitney). Five early mechanical failures were excluded from this analysis.     

Fracture-dislocation of the hip with ipsilateral femoral neck fracture

. Fracture-dislocation of the hip associated with fracture of the femoral neck and intrapelvic intrusion of the femoral head is a rare injury. In this case we performed open reduction for the femoral neck fracture, and external fixation for the pelvic fracture by Judet-Meyers method. As a result the patient has not complained of pain, although he developed arthrokleisis due to ectopic ossification around the femoral head, as well as femoral head necrosis. Résumé. Nous rapportons un cas de fracture-luxation de la tête fémorale avec migration dans le bassin chez un homme de 25 ans. La réduction a été réalisée par fixation vis-plaque, le patient ne présente actuellement aucune douleur, pas d'arthrose de la hanche, ni de nécrose de la tête fémorale, mais il a une petite raideur due à des ossifications péri-articulaires de sa hanche. Cinq ans après, le patient est resté asymptomatique.     

骨质疏松女性股骨颈骨折与股骨转子间骨折的髋部骨密度差异分析

目的明确骨质疏松女性股骨颈骨折与股骨转子间骨折的髋部骨密度差异,探讨骨质疏松患者发生髋部骨折(股骨颈骨折、股骨转子间骨折)与骨折部位骨密度的相关性。方法回顾性分析2015年1月1日至2016年12月31日期间于福建省某三级甲等医院的住院治疗的骨质疏松及髋部骨质疏松性骨折患者172例,其中无病史的原发骨质疏松患者109例、骨质疏松性股骨颈骨折患者39例、骨质疏松性转子间骨折24例。分别统计3组患者年龄、体质指数、糖尿病患病情况、骨折侧别、髋部各部位骨密度、血清Ⅰ型胶原交联C末端肽(C-terminal crosslinking telopeptide of type Ⅰ collagen,CTX)、Ⅰ型原胶原N-端前肽(procollagen type ⅠN propeptide,PINP)、25羟基维生素D(25-OH-D)。分别进行三组间及两两组间比较。结果三组间年龄、体质指数、糖尿病患病率差异无统计学意义(F=2.667,P=0.072; F=0.882,P=0.416;χ~2=3.216,P=0.232),股骨颈骨折组与股骨转子间骨折组组间骨折侧别差异无统计学意义(χ~2=0.958,P=0.328),三组间髋部Ward区骨密度差异无统计学意义(F=2.937,P=0.056),髋部骨密度比较,股骨颈、股骨大转子、股骨转子间、髋部整体差异有统计学意义(F=7.825,P=0.001; F=8.668,P0.001; F=9.657,P0.001)。股骨颈骨折组、转子间骨折组股骨颈、股骨大转子、股骨转子间、髋部整体骨密度均小于骨质疏松组,差异均有统计学意义(P0.05);股骨颈骨折组与转子间骨折组股骨颈、大转子、转子间、髋部整体骨密度差异均无统计学意义(P0.05)。三组间β-CTX、P1NP、维生素D差异均有统计学意义(P0.05)。股骨颈骨折组、转子间骨折组β-CTX、维生素D均小于骨质疏松组,差异均有统计学意义(P0.05);转子间骨折与骨质疏松组P1NP差异无统计学意义,股骨颈骨折组与转子间骨折组股骨颈、大转子、转子间、髋部整体骨密度差异均无统计学意义(P0.05)。结论女性骨质疏松患者发生髋部骨折的类型可能并不取决局部的骨密度,可能与骨微结构等因素相关,要得到明确、可靠的结果仍需进一步研究证实。     

Surgical treatment of intertrochanteric hip fractures with associated femoral neck fractures using a sliding hip screw

OBJECTIVE: The purpose of this study was to report the results of surgical treatment of a subset of intertrochanteric fractures with posteromedial comminution and extension of the fracture line into the femoral neck using a sliding hip screw. DESIGN: Retrospective review. SETTING: Level I county trauma center. PATIENTS: Twenty-nine fractures (8%) with this pattern were identified from 381 intertrochanteric hip fractures treated at a single institution over a 10-year period. Nine patients were excluded (2 died, 7 had incomplete radiographic follow-up), leaving 20 patients for assessment. INTERVENTION: All fractures were treated with a sliding hip screw. MAIN OUTCOME MEASUREMENTS: Radiographs at a mean follow-up of 17 months were recorded as demonstrating: 1) fixation failure; 2) fracture union; or 3) fracture nonunion. The tip-apex distance, amount of lag screw collapse, screw position in the femoral head, and adequacy of reduction were determined. RESULTS: Treatment failed according to these radiographic measures in 5 of 20 (25%) fractures. Failures included fracture nonunion (1 case), lag screw cutout (2 cases), and combined nonunion/lag screw cutout (2 cases). All 5 failures had complete collapse of the lag screw, whereas 4 of the 15 successfully treated fractures had complete collapse. The amount of collapse was significantly greater for the treatment failures (mean, 38 mm) than in the successfully treated hips (mean, 20 mm). There was no significant association between treatment success or failure and tip-apex distance, lag screw position, and adequacy of reduction. CONCLUSION: We conclude that intertrochanteric hip fractures with associated femoral neck fractures should not be managed with a standard sliding hip screw.     

股骨颈骨密度和股骨颈轴长与老年 髋部骨折的关系

目的 探讨股骨颈骨密度、股骨颈轴长与髋部骨折的关系，了解股骨颈骨密度、股骨颈轴长预测骨折的能力。方法 通过双能Ｘ线吸收骨密度测量仪测量髋部骨折组患者和同龄男女非骨折对照组的股骨颈轴长、股骨颈骨密度，分析比较两种测量指标预测股骨颈骨折的敏感性。结果 不同性别骨折组患者的股骨颈骨密度均明显低一南年龄、同性别对照组，差异有非常显著性意义（Ｐ〈０．０１），而骨折组与非骨折组男女股骨颈轴和莘差异无显著性意义     

Rarefied femoral neck trabecular patterns, fracture displacement, and femoral head vitality in femoral neck fractures

Before operation, 99mTc-MDP scintimetry was performed in 103 patients with femoral neck fractures. There was a significant correlation (r = 0.63, p less than .01) between osteoporosis and fracture displacement, but no correlation (r = 0.07, p greater than .01) between femoral neck trabecular bone patterns and femoral head viability and no correlation (r = 0.11, p less than .01) between fracture displacement and femoral head viability.     

Larger femoral periprosthetic bone mineral density decrease following total hip arthroplasty for femoral neck fracture than for osteoarthritis: A prospective,observational cohort study

Studies on patients with degenerative joint disease of the hip show that femoral periprosthetic bone mineral decreases following total hip arthroplasty. Scarcely any osteodensitometric data exist on femoral neck fracture (FNF) patients and periprosthetic bone remodelling. In two parallel cohorts we enrolled 87 patients (mean age, 72 ± 12 years; male:female ratio, 30:57) undergoing total hip arthroplasty for either primary osteoarthritis (OA) of the hip (n = 37) or for an acute FNF (n = 50) and followed them for a mean of 5.4 years. Outcomes were bone mineral density (BMD) changes in the periprosthetic Gruen zones 1–7, the incidence of periprosthetic fractures and clinical outcome. The bone mineral loss in the fracture group was more than twice that of the osteoarthritis group, ?16.9% versus ?6.8% (p = 0.004). The incidence of periprosthetic fractures was 12% (6/50) in the fracture cohort compared with none (0%) in the OA cohort (p = 0.03). Periprosthetic bone mineral loss following total hip arthroplasty is significantly greater in patients who are treated for acute FNF than in OA patients. This decrease of BMD follows a different pattern with the FNF patients losing larger proportions of bone in Gruen zones 1, 2, 6, and 7 while the OA patients tend to have larger losses only in zones 1 and 7. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:504–512, 2015.

     

Bone impregnated hip screw in femoral neck fracture: Clinicoradiological results

Background:

Femoral neck fractures are treated either by internal fixation or arthroplasty. Usually, cannulated cancellous screws are used for osteosynthesis of fracture neck of femur. The bone impregnated hip screw (BIHS) is an alternative implant, where osteosyntehsis is required in femoral neck fracture.

Materials and Methods:

The BIHS is a hollow screw with thread diameter 8.3 mm, shank diameter 6.5 mm and wall thickness 2.2 mm and holes in the shaft of the screw with diameter 2 mm, placed in a staggered fashion. Biomechanical and animal experimental studies were done. Clinical study was done in two phases: Phase 1 in a group of volunteers, only with BIHS was used in a pilot study and phase 2 comparative study was done in a group with AO cannulated screws and the other group treated with BIHS.

Results:

In the phase 1 study, out of 15 patients, only one patient had delayed union. In phase 2, there were 78 patients, 44 patients in BIHS showed early union, compared to the rest 34 cases of AO cannulated screws Out of 44 patients with BIHS, 41 patients had an excellent outcome, 2 had nonunions and one implant breakage was noted.

Conclusions:

Bone impregnated hip screw has shown to provide early solid union since it incorporates the biomechanical principles and also increases the osteogenic potential and hence, found superior to conventional cannulated cancellous screw.     

Secondary total hip replacement after fractures of the femoral neck

We studied the rate of revision in 84 consecutive total hip replacements performed for failed osteosynthesis of femoral neck fractures and compared it with that for primary arthroplasty for osteoarthritis. The age and sex adjusted risk of prosthetic failure was 2.5 times higher after failure of fixation, but all the excess risk was in patients over 70 years of age. There were radiographic signs of loosening of the femoral component at five to 12 years after secondary arthroplasty in six of 33 survivors. In general, the results of secondary replacement were no worse than those obtained after primary arthroplasty for femoral neck fracture. We consider that internal fixation should be the primary procedure: total hip replacement is a safe secondary procedure when osteosynthesis fails.