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In recent years, atypical femoral fractures and osteonecrosis of the jaw have emerged as potential complications of long-term bisphosphonate therapy; osteonecrosis of the jaw has also been reported in patients receiving high doses of denosumab. The pathophysiology of both conditions is poorly defined, and the underlying mechanisms are likely to differ. The initiation of atypical fractures in the lateral femoral shaft suggests that reduced tensile strength, possibly secondary to alterations in the material properties of bone resulting from low bone turnover, may be an important pathogenetic factor. Osteonecrosis of the jaw is characterised by infection, inflammation, bone resorption and bone necrosis, but the sequence in which these occur has not been established. However, the observation that bone resorption occurs in close proximity to microbial structures suggests that infection may be the most important trigger, often as a result of dental disease. Other possible pathogenetic factors include suppression of bone turnover, altered immune status and adverse effects of bisphosphonates on the oral mucosa.

Purpose: Kienböck disease is characterized by avascular necrosis of the lunate bone, which is usually progressive without treatment. This study examined lunate core decompression for its treatment potential., Methods: We surgically treated 20 patients with stage 1 to 3b Kienböck disease with lunate core decompression. We evaluated pain, range of motion, functional disability, and radiographic indices in these patients at baseline and 5 years after surgery., Results: The mean age of the patients was 29 years; 16 were men. Ten patients had Lichtman stage 1 disease, 6 had stage 2 disease, 3 had stage 3a, and 1 had stage 3b disease. Range of motion scores showed meaningful improvement. Two patients did not improve with this technique and were revised with radial shortening procedures., Conclusions: Lunate core decompression is a simple surgical procedure that is effective in the treatment of Kienböck disease., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry. Data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry were used as an example., Methods: A case-control matching analysis using the risk-set method was conducted to identify two groups of patients with type 1 Gaucher disease in the ICGG Gaucher Registry: patients with avascular osteonecrosis (AVN) and those without AVN. The frequency distributions of gender, decade of birth, treatment status, and splenectomy status were presented for cases and controls before and after matching. Odds ratios (and 95% confidence intervals) were calculated for each variable before and after matching., Results: The application of case-control matching methodology results in cohorts of cases (i.e., patients with AVN) and controls (i.e., patients without AVN) who have comparable distributions for four common parameters used in subject selection: gender, year of birth (age), treatment status, and splenectomy status. Matching resulted in odds ratios of approximately 1.00, indicating no bias., Conclusions: We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries.

Avascular necrosis of bone may affect specific areas of the body where the blood supply to the bone or part of the bone is vulnerable to injury or disease. In the carpal scaphoid, it can find this entity consequent a trauma, microtrauma, or fractures, especially in the proximal pole (Preiser in Fortschr Geb Roentgenstr 15:189-197, 1910), associated with a systemic disease, steroid ingestion (Ferlic and Morin in J Hand Surg-A 14:13-16, 1989), chemotherapy (Green in Hand Clinic 3:163-168, 1987) or a hypoplastic scaphoid (Gunal et al., in J Hand Surg-B 20(6):736-740, 1995). Preiser's disease is a rare entity and is commonly associated with avascular necrosis of the scaphoid without fracture or trauma. A case of bilateral idiopathic avascular necrosis of the scaphoid is reported.

Osteoradionecrosis of the mandible is a serious complication following radiation therapy with or without surgical intervention for malignancies of the head and neck. The acknowledged clinical presentation of osteoradionecrosis is pain, fistulae of mucosa or skin, complete devitalization of bone and pathological fractures. Radiation-induced fibrosis is an irreversible pathological process, which leads to damages in lung, skin, intestine, and pelvic cavity after radiotherapy. Studies have proved that radiation-induced fibrosis is involved in the pathological onset, development, maintenance of osteoradionecrosis and there is dose-effect relationship between them, so the authors hypothesize that radiation-induced fibrosis plays an important role in osteoradionecrosis. Studies need to perform to look for more efficient methods of managing and preventing the osteoradionecrosis., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

The influence of intramedullary (IM) and extramedullary (EM) femoral cutting guides on survivorship of total knee arthroplasty was studied in 6726 total knee arthroplasty guided by either an IM (4993 knees) or EM (1733 knees) system. Fifteen-year survivorship of the 2 cohorts showed no statistically significant difference (EM 97.9% vs IM 98.5%; P = .2500, log rank). Medial bone collapse comprised the highest proportion of all failure modes for both groups (0.35% vs 0.40%, respectively, P = .6731, Cox regression). Mean tibiofemoral (overall) anatomical alignment was statistically more accurate in the IM group (IM 4.6° [± 2.2°] valgus vs EM 5.1° [± 3.1°] valgus; P < .0001). The mean tibial alignment was 90.5° (± 3.0) and 90.3° (± 2.2) (P = .0077). The EM group had a significantly larger tibial component alignment variance (SD(2)) than the IM group. No statistical difference in postoperative Knee Society scores, pain, or stair-climbing abilities was found. The choice of either alignment system should be determined by the patient's anatomy; however, the overall alignment is not as precise using the extramedullary system., (Copyright © 2011. Published by Elsevier Inc.)

For the patient (and the surgeon) the ideal wrist is one that has good mobility, however very often the optimal surgical treatment is one that provides effective pain relief. The patient must be informed of the potential complications and limitations of each procedure. The patient's psychological profile and functional requirements will determine how well he/she adapts to the changes. Also, each surgeon has beliefs and personal experiences that influence the treatment decision and final result. Proximal row carpectomy (PRC) and the Watson procedure are two reference operations for osteoarthritis secondary to scapholunate instability and scaphoid non-union (SLAC and SNAC). Beyond the early complications and drawbacks specific to each, they provide good results that are maintained over time. PRC, which can be performed up to Stage II, is mainly indicated in patients with moderate functional demands, while the Watson procedure is more often done on a patient who performs manual labour, as long as the radiolunate joint space is maintained. Complete denervation is effective in three out of four cases and preserves the remaining mobility. Because of its low morbidity, the procedure can be suggested in patients with a mobile wrist and low functional demands or in older patients, independent of their wrist mobility. Total wrist fusion is not only a rescue procedure. For a young patient who performs heavy manual labour with extensive osteoarthritis and progressive forms of Kienböck's disease, this procedure provides the greatest chance of returning to work and not being socially outcast. The role of osteochondral autografts, implants and wrist prostheses in the treatment arsenal need to be better defined., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Bisphosphonates are common first line medications used for the management of benign bone disease. One of the most devastating complications associated with bisphosphonate use is osteonecrosis of the jaws which may be related to duration of exposure and hence cumulative dose, dental interventions, medical co-morbidities or in some circumstances with no identifiable aggravating factor. While jaw osteonecrosis is a devastating outcome which is currently difficult to manage, various forms of delayed dental healing may be a less dramatic and, therefore, poorly-recognised complications of bisphosphonate use for the treatment of osteoporosis. It is hypothesised that long-term (more than 1 year's duration) bisphosphonate use for the treatment of post-menopausal osteoporosis or other benign bone disease is associated with impaired dental healing., Methods/design: A case-control study has been chosen to test the hypothesis as the outcome event rate is likely to be very low. A total of 54 cases will be recruited into the study following review of all dental files from oral and maxillofacial surgeons and special needs dentists in Victoria where potential cases of delayed dental healing will be identified. Potential cases will be presented to an independent case adjudication panel to determine if they are definitive delayed dental healing cases. Two hundred and fifteen controls (1:4 cases:controls), matched for age and visit window period, will be selected from those who have attended local community based referring dental practices. The primary outcome will be the incidence of delayed dental healing that occurs either spontaneously or following dental treatment such as extractions, implant placement, or denture use., Discussion: This study is the largest case-controlled study assessing the link between bisphosphonate use and delayed dental healing in Australia. It will provide invaluable data on the potential link between bisphosphonate use and osteonecrosis of the jaws.

Of various surgical treatments, radial shortening for patients with negative ulnar variance and radial wedge osteotomy (radial closing osteotomy) for patients with 0 or positive ulnar variance are widely accepted for the treatment of Kienböck disease. Long-term follow-up studies have shown more than 10 years lasting satisfactory pain relief, as well as an increase in wrist range of motion and grip strength. As representative surgical procedures, the techniques of radial shortening by transverse osteotomy, using a locking compression plate for internal fixation, and radial wedge osteotomy by step-cut osteotomy, using a small dynamic compression plate or locking compression plate, are described. One important point of radial wedge osteotomy is that resection of simple wedge bone yields a decrease in ulnar variance; therefore, we recommend trapezoidal bone resection with ulnar height of 1 mm for transverse osteotomy at the metaphysis and ulnar height of 2 mm for step-cut osteotomy at the distal fourth of the radius.

The etiology of Kienböck disease is still unknown and, consequently, the ideal treatment is in doubt. Many different hypotheses have been suggested. There are reasons to believe that there are mechanical, vascular, and metabolic factors predisposing to the disease, and probably some factors triggering the development of the process. Among mechanical factors, the short ulna has been thought to be the most relevant. However, presently there are insufficient data to support a significant association between negative ulnar variance and Kienböck disease. With regard to vascular factors, anatomical studies have shown consistent dorsal and palmar arteries entering the bone, and thus, the most likely site for vascular impairment may be at the subchondral level. Many triggering factors have been proposed during the past years, but until this is truly clarified, finding the real cause of Kienböck disease will continue to be a real challenge.

Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined., (© 2010 Australian Dental Association.)

The goals of treatment in Kienböck disease include preservation of wrist function, maintaining normal wrist kinematics, and revascularization of the necrotic lunate when and if possible. A variety of pedicled vascularized bone graft options exist and include but are not limited to pedicled grafts from the volar radius, dorsal radius, metacarpal heads or bases, and pisiform. Of the various treatment options, pedicled vascularized bone grafts from the dorsal distal radius based on the fourth and fifth extensor compartment arteries has been successful in the revascularization of the necrotic lunate at our institution. Vascularized bone grafting is an attractive alternative to conventional bone grafting by improving the local biological environment and thereby promoting revascularization. Recent advances in the anatomy and physiology of vascularized pedicled bone grafts have increased our ability to apply them to the treatment of Kienböck disease. The purpose of this article is to describe the various types of pedicled vascularized bone graft available, to detail the vascular anatomy of the dorsal distal radius, and to describe the surgical technique of our preferred vascularized bone graft (the fourth+fifth extensor compartment artery graft). In addition, the indications, contraindications, and outcomes are described.

Bisphosphonates are used in the treatment of hypercalcemia of malignancy, skeletal complications associated with metastastic bone disease, Paget's disease, and osteoporosis. Osteonecrosis of the jaw (ONJ) is a recently described clinical condition that has been associated with the use of nitrogen-containing bisphosphonates. Reports describing this entity first appeared in the literature in 2003. While there have been significant numbers of case reports and a limited number of retrospective and prospective studies examining risk factors associated with ONJ, the pathophysiology of this condition remains elusive. In this review, we explore proposed mechanisms underlying ONJ development and identify potential areas for future investigation., (© 2011 New York Academy of Sciences.)

Background: To investigate the relationship between chemokines and cytokines and osteonecrosis in Gaucher disease, we conducted multiplex assays in a cohort of 100 adult patients., Methods: Mean age was 45 years (18-86); 92 Gaucher patients received imiglucerase (median duration 8 years (2-18)). Forty-three had experienced osteonecrosis (ON), and eight had ON despite enzyme therapy. Serum cytokines/chemokines were determined by fluorimetric bead arrays in samples from Gaucher patients and healthy volunteers (10 males and 10 females). Intra-assay and inter-assay coefficients of variation were 2%-9.8% and 5.6%-15%, respectively., Results: VEGF and CCL5/RANTES did not differ between Gaucher and control samples. Concentrations of CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, CXCL8/IL-8, IL-1ra and CCL18/PARC were elevated in Gaucher patients (p<0.05 for each). Median CCL4/MIP-1β, CXCL8/IL-8, CCL5/RANTES and CCL18/PARC concentrations were greater in the 43 osteonecrosis patients (88.6 pg/mL, 30.5 pg/mL, 89.6 ng/mL and 434 ng/mL, respectively) compared with the 57 patients who had no evidence of osteonecrosis (medians of 59.4, 13.3, 62.7 and 283, respectively, p<0.05). Moreover, the eight patients with ON despite imiglucerase had median concentrations of CCL3/MIP-1α, CCL4/MIP-1β, CXCL8/IL-8, CCL5/RANTES and CCL18/PARC (73.2, 120.9, 36.3 pg/mL, 105 and 767 ng/mL, respectively), which significantly exceeded the values in 84 patients now free of ON (52.3, 71.2, 16.5 pg/mL, 69.5 and 315 ng/mL, respectively, p<0.05). Treatment exposures were similar., Conclusion: Numerous serum cytokines are elevated in Gaucher disease. CCL18/PARC, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES and CXCL8/IL-8 are potential biomarkers of osteonecrosis and may allow prediction of this disabling complication., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Periprosthetic bone changes following hip arthroplasty are yet to be completely described. The material consisted of imagistic records (X-ray films, CT and MRI scans) and of acetabular bone tissue sampled from 14 cases with femoral head prosthesis and revision of the prosthesis fixed and decalcified in Duboscq-Brazil solution and stained with Hematoxylin and Eosin, trichrome van Gieson and trichrome Masson. Acetabular bone is home of a great variety of morphological changes that can be divided in degenerative and regenerative changes seen in both compact and trabecular components but only inside the maximal pressure area of the acetabular roof. Our preliminary morphological study revealed the existence of an adaptation effort to the mechanical stress materialized through a dynamic process of bone remodeling in the maximal pressure area.

Gaucher disease (GD), the most prevalent lysosomal storage disorder, affects multiple organ systems. Patients with non-neuronopathic (type 1) GD, the most common form of GD, present with hepatomegaly, splenomegaly, anemia, bleeding tendencies, thrombocytopenia, skeletal pathologies, growth retardation, and, in severe cases, pulmonary disease. The bone manifestations include bone infarcts, avascular bone necrosis, lytic lesions, osteosclerosis, fractures due to osteopenia or osteoporosis, and rarely acute osteomyelitis. Bone pain of varying intensity, fractures, and progressive joint collapses may cause impaired mobility and performances status, and increased morbidity. Enzyme replacement therapy and substrate reduction therapy have demonstrated to have beneficial effects on bone pain, bone crises, and the extent of osteoporosis. This review article gives an overview of the clinical appearance of bone pathology in GD, the possible pathophysiological mechanisms, diagnostic approaches, and the therapeutic effects of enzyme replacement therapy, substrate reduction therapy, and bone specific therapies as evaluated in current literature.

Background: The treatment of end-stage hip disease in very young patients is controversial, with advocates for nonoperative treatment, hip arthrodesis and replacement procedures. The functional improvements in this group of patients are not well documented and whether the condition for which the surgery is performed influences function., Questions/purposes: We determined whether (1) modern THA provides major functional improvements; (2) disease-specific factors impact the magnitude of improvement; (3) these procedures are associated with early failures and complications; and (4) radiographically secure implant fixation is achieved with contemporary implants., Methods: We retrospectively reviewed 88 patients (102 hips) who had THA and were 25 years or younger at surgery. The most common diagnoses were osteonecrosis (44%) and secondary osteoarthritis (41%). All patients received a cementless socket of varying designs and all except five a cementless stem. Demographic data, Harris hip score, and Charnley classification were recorded. Radiographic evaluation was used to determine implant fixation. We identified complications and failure mechanisms. The minimum followup was 2 years (median, 4.2 years; range, 2-16 years)., Results: The 95 nonrevised hips were followed clinically an average of 61 months. The mean Harris hip scores improved from 42 preoperatively to 83 postoperatively. Lower Harris hip scores were associated with systemic disease (Charnley Class C). Seven hips (7%) underwent revision. There were nine (9%) major complications. One hundred percent of femoral stems and 98% of acetabular components were well-fixed at last followup., Conclusion: Contemporary total hip arthroplasty in patients 25 years of age and younger is associated with improved hip function, and secure fixation of cementless implants at early followup.

Purpose: More studies have begun to investigate properties of tissue obtained from patients with osteonecrosis of the jaw (ONJ). Because of the relatively low incidence of ONJ, these studies necessitate the use of specimens from patients who have had ONJ for various durations. The goal of this study was to determine if properties, specifically bone morphology assessed by microcomputed tomography, were influenced by the duration of ONJ., Materials and Methods: Sequestra from 31 patients with confirmed ONJ for 3 weeks to 42 months before obtaining the tissue were scanned using microcomputed tomography to determine bone volume/tissue volume and bone surface/tissue volume., Results: There was no significant correlation between the sequestra bone morphology (bone volume/tissue volume or bone surface/tissue volume) and the duration of ONJ., Conclusion: The findings indicated that studies should not be concerned about assessing tissue properties from patients who have had ONJ for different durations. In addition, the lack of difference in morphology with continued duration of ONJ suggests that most changes to bone tissue occur early in the disease progression., (Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Reports of coexisting avascular necrosis of more than one carpal bone are rare. We report coexisting avascular necrosis of the scaphoid and lunate in a 56-year-old woman with no history of using steroids or injury. We treated her with a radioscapholunate fusion with two angled 2.4 mm distal radius plates to stabilise the locking plate. At her 12-month follow up there was no evidence of non-union.

Bisphosphonate treatment and its aetiopathogenic association with aseptic osteonecrosis of the jaw is one of the more prominent public health issues today. The aim of this review is to see into the mechanisms of bisphosphonate effects on bones described in literature (anti-osteoclastic activity, cytotoxicity, antiangiogenesis, genetic factors, and imbalance between osteoclasts and osteoblasts). Bisphosphonate treatment is the dominant cause of jaw necrosis. Epidemiological data show an exclusive incidence of osteonecrosis of the jaw in patients who took one or a combination of nitrogen-containing bisphosphonates. Risk factors vary by the bisphosphonate potency (particularly risky are the highly potent pamidronate and zoledronate, which are given intravenously), dosage, duration of treatment, and the illness. Jaw necrosis is most common in oncology patients, and only 5 % in patients with osteoporosis. From a dental-medical point of view, a good oral health is important because osteonecrosis often appears after a periodontal or oral surgical procedure.

Background: Osteonecrosis is a major treatment complication of pediatric leukemias owing to its potential to cause joint deterioration. Because of potential long-term effects of osteonecrosis on joints, information regarding its progression and collapse in different patients can be used to identify high-risk groups, advise the patients and parents of this complication, and potentially consider the risk for development of osteonecrosis in planning primary treatment., Questions/purposes: We therefore determined: (1) the incidence of joint collapse and/or pain in young patients with hematologic malignancies diagnosed with ON of the knee; (2) risk factors associated with collapse; and (3) the relationship between size and location of osteonecrotic knee lesions and the likelihood of joint collapse., Patients and Methods: We retrospectively reviewed 109 patients with hematologic malignancies and MRI-confirmed knee osteonecrosis. The median age was 11.5 years (range, 2.3-18.8 years) at primary diagnosis of hematologic malignancy and a median age of 13.4 years (range, 2.7-23.3 years) at diagnosis of osteonecrosis of the knee. For analyses, we used the first and last MR images. Minimum clinical followup was 2.3 years after diagnosis of knee osteonecrosis (median, 6 years; range, 2.3-7.17 years)., Results: Joint collapse occurred in 22% (24 of 109). Older age, pain at osteonecrosis presentation, and lesions extending to the articular surface of distal femoral epiphyses were associated with joint collapse., Conclusions: Younger patients and those without extensive femoral epiphyseal involvement have a better prognosis for osteonecrosis of the knee., Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

The purpose of this study was to investigate factors affecting the short-term outcome of primary total hip arthroplasty (THA) and develop a multivariate regression equation to predict the short-term outcome of primary THA. Prospectively collected data for 101 primary THAs performed at a single institution were used in this study. Twelve independent variables were analyzed via correlation and multivariate regression analyses. Correlation analyses showed that three variables significantly influenced Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function (PF) score at minimum follow-up of 1 year: preoperative WOMAC PF score (P < .0001), sex (GN, P = .0159), and the presence of preoperative comorbidities (CMB, P = .0246). Multivariate regression analysis yielded the following equation: Outcome = PF0.45 - GN9 + CMB8 + 62, which can be used to predict the general short-term outcome of primary THA., (Copyright 2010 Elsevier Inc. All rights reserved.)

Four patients underwent laryngoscopy and general anesthesia surgery without apparent perioperative complications. Within days of their procedure, throat and mouth pain were reported and intraoral examination in all cases revealed exposed bone in the posterior mandible. The sequestra were easily removed and healing was uneventful. These lesions are likely associated with localized oral trauma during intubation causing periosteal damage, compromised blood supply, and subsequent bone necrosis. Because trauma to the mylohyoid ridge during intubation is likely more common than previously appreciated, anesthesiologists should be aware of this potential complication and refer patients to a specialist for management.

Purpose: To investigate the characteristics of nonunion and avascular necrosis following phalangeal neck fracture in children., Methods: A cohort of all pediatric phalangeal neck fractures complicated by nonunion, with or without avascular necrosis of the phalangeal head, over the last 10 years was reviewed retrospectively. The following data were documented: age, gender, fracture site, mechanism of injury, fracture type, presence of digital ischemia, initial management, and outcome., Results: Our database of phalangeal neck fractures in children over the last 10 years included 215 fractured digits. Of these, 4 developed nonunion (group A) and 8 developed nonunion with avascular necrosis (group B). All patients in group A were young children (mean age, 2.5 y) with fractured thumbs, initially managed by closed reduction and splinting. The fractures redisplaced and failed to unite, resulting in instability that was later treated by bone grafting and stabilization with a K-wire. Patients in group B were older children (mean age, 5.6 y) and 7 of 8 had finger fractures. All 8 patients presented with stiffness of the affected joint, and no further surgery was performed., Conclusions: When nonunion occurs following pediatric phalangeal neck fractures, it usually affects the thumb and presents with thumb instability, and bone grafting is often required to achieve union. In contrast, avascular necrosis following phalangeal neck fractures usually affects the little finger and presents with stiffness, and hence, further surgery is not often required short term, although the long-term result after skeletal maturity is unknown., Type of Study/level of Evidence: Therapeutic IV., (Copyright 2010. Published by Elsevier Inc.)

The peripheral cortex of a vertebral body affected by Kümmell's disease is not always intact, resulting in high risk for cement leakage. This study used modified techniques to avoid cement extravasation and dislodgment and investigated the feasibility and efficacy of kyphoplasty for treatment of Kümmell's disease. Between May 2006 and May 2008, 21 consecutive patients with Kümmell's disease underwent kyphoplasty with modified techniques. Each patient was assessed preoperatively with standard examinations and imaged with dynamic radiographs, 3-dimensional computed tomography scans, and magnetic resonance imaging. A visual analog scale (VAS) and the Oswestry Disability Index were used to measure pain and disability pre- and postoperatively and at 6- and 12-month follow-up. One patient had cement leakage into the disk space but no clinical symptoms. There were no cases of cement dislodgment at follow-up. Comparison of the pre- vs postoperative VAS scores revealed significant differences (P<.05), whereas VAS scores at 6- vs 12-month follow-up were similar. The Oswestry Disability Index scores varied from 62.3%+/-15.1% preoperatively to 35.2%+/-12.1% postoperatively (P<.05). This improvement in scores was still present at 6- and 12-month follow-up. At 6- and 12-month follow-up, maintenance of height restoration and kyphotic deformity correction was found. Kyphoplasty may be a relatively safe and effective method for treatment of Kümmell's disease when modified techniques are used to prevent cement leakage and dislodgment., (Copyright 2010, SLACK Incorporated.)

Transient bone marrow edema syndrome (TBMES) is a disorder with unknown etiology and must be included in the differential diagnosis of hip pain. TBMES generally has a good prognosis but, it can be result in avascular necrosis (AVN). We present two cases diagnosed with TBMES, one of whom experienced full remission and the other who developed AVN.

Despite the increasing success of transplantation, graft recipients experience a high burden of musculoskeletal symptoms that may hinder quality of life. Post-transplant musculoskeletal problems may result from sequelae of the organ dysfunction that indicated the transplant or from the subsequent anti-rejection therapy. Rheumatology consultants need to be familiar with the spectrum of musculoskeletal syndromes presenting in these unique patients and their appropriate treatment in the context of complex drug regimens and immunosuppression., (Published by Elsevier Ltd.)

Multiple factors have been implicated in the development of osteonecrosis of the femoral head (ONFH). In particular, non-traumatic ONFH is directly or indirectly related to injury of the vascular supply to the femoral head. Thus, hypoxia in the femoral head caused by impaired blood flow may be an important risk factor for ONFH. In this study, we investigated whether genetic variations of angiogenesis- and hypoxia-related genes contribute to an increased risk for the development of ONFH. Candidate genes were selected based on known hypoxia and angiogenesis pathways. An association study was performed using an Affymetrix Targeted Genotyping 3K Chip array with 460 ONFH patients and 300 control subjects. We showed that single nucleotide polymorphisms (SNPs) in the genes TF, VEGFC, IGFBP3, and ACE were associated with an increased risk of ONFH. On the other hand, SNPs in the KDR and NRP1 genes were associated with protection against ONFH. The most important finding was that one SNP (rs2453839) in the IGFBP3 gene was significantly associated with a higher risk of ONFH (P=0.0061, OR 7.74). In subgroup analysis, most candidate gene variations that were associated with ONFH occurred in the idiopathic subgroup. Among other SNPs, ACE SNPs were associated with steroid-induced ONFH (P=0.0018-0.0037, OR>3). Collectively, our findings suggest that genetic variations in angiogenesis- and hypoxia-related genes may help to identify susceptibility factors for the development of ONFH in the Korean population.

The aim of this study was to evaluate a novel animal model of bisphosphonates-associated osteonecrosis, which realistically recapitulates the same pathological human condition. Five Wistar rats were given intravenous zoledronic acid 0.04 mg once a week for 5 weeks. After 2 weeks, the animals underwent the extraction of an upper molar, producing a 4 mm-diameter bone defect on the same site. After 7 weeks from the extraction, the animals were clinically examined and a bone scintigraphy was carried out. After an additional week, the rats were killed and both Computerized Tomography and histological analysis were performed. Five rats, not treated with zoledronic acid and exposed to the same surgical treatment, were used as controls. At 7 weeks after the extraction, all the rats treated with zoledronic acid showed expansion of the defect and bone exposure. These features were confirmed by bone scintigraphy. The rats of the control group demonstrated epithelialization of the bone defect and a normal uptake of the contrast medium during the scan. The Computerized Tomography scan disclosed irregularity of the cortical margin and bone destruction, which were not evident in the control group. On microscopy, the samples showed necrotic bone, loss of osteocytes and peripheral resorption without inflammatory infiltrate, while the controls showed normal bone healing. The rat treated with zoledronic acid can be considered a novel, reliable and reproducible animal model to understand better the pathophysiology of osteonecrosis of the jaw and to develop a therapeutic approach.

Purpose: Nitrogen-containing bisphosphonates (NBPs) have powerful anti-bone-resorptive effects (ABREs). However, recent clinical applications have disclosed an unexpected side effect, osteonecrosis of the jaw. We previously found in mice that etidronate (a non-NBP), when coadministered with alendronate (an NBP), inhibited the latter's inflammatory effects. However, etidronate also reduced the ABRE of alendronate. The present study examined in mice the modulating effects of etidronate on the inflammatory and necrotic actions of zoledronate (the NBP with the strongest anti-bone-resorptive activity and the highest incidence of osteonecrosis of the jaw) and on ABREs of various NBPs including zoledronate., Materials and Methods: NBPs were subcutaneously injected into ear pinnas of mice and ensuing inflammation and necrosis at the site of the injection were evaluated. ABREs of NBPs were evaluated by analyzing sclerotic bands induced in mouse tibias., Results: Coinjection of etidronate reduced inflammatory and necrotic reactions induced by zoledronate, and also reduced the amount of zoledronate retained within the ear tissue. When both agents were intraperitoneally injected, etidronate reduced the ABRE of zoledronate and those of other NBPs. Notably, etidronate reduced the ABRE of zoledronate even when this non-NBP was injected 16 hours after the injection of zoledronate. Bone scintigram indicated that etidronate reduced the amount of zoledronate that had already bound to bone., Conclusions: These results suggest that etidronate may 1) inhibit the entry of NBPs into cells related to inflammation and/or necrosis, 2) inhibit the binding of NBPs to bone hydroxyapatite, 3) at least partly eliminate (or substitute for) NBPs that have already accumulated within bones, and thus 4) if used as a substitution drug for NBPs, be effective at treating or preventing NBP-associated osteonecrosis of the jaw., (Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Osteonecrosis is commonly present in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Treatment of this condition remains extremely controversial. We present a treatment strategy of avascular necrosis of the knee in a patient with catastrophic antiphospholipid syndrome with a history of SLE and APS. Aggressive treatment with 12 rounds of plasmapheresis, intravenous immunoglobulin, rituximab, and cyclophosphamide led to the patient's recovery with no recurrence of symptoms during 16 months of follow up. In this report, we further discuss the pathogenesis of osteonecrosis and current understanding of the treatment of this disease.

In the past decades, considerable efforts have been made to propose experimental and clinical treatments for articular cartilage defects. Yet, the problem of cartilage defects extending deep in the underlying subchondral bone has not received adequate attention. A profound understanding of the basic anatomic aspects of this particular site, together with the pathophysiology of diseases affecting the subchondral bone is the key to develop targeted and effective therapeutic strategies to treat osteochondral defects. The subchondral bone consists of the subchondral bone plate and the subarticular spongiosa. It is separated by the cement line from the calcified zone of the articular cartilage. A variable anatomy is characteristic for the subchondral region, reflected in differences in thickness, density, and composition of the subchondral bone plate, contour of the tidemark and cement line, and the number and types of channels penetrating into the calcified cartilage. This review aims at providing insights into the anatomy, morphology, and pathology of the subchondral bone. Individual diseases affecting the subchondral bone, such as traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis are also discussed. A better knowledge of the basic science of the subchondral region, together with additional investigations in animal models and patients may translate into improved therapies for articular cartilage defects that arise from or extend into the subchondral bone.

Spontaneous osteonecrosis of the knee was originally described as a distinct disorder in 1968. Characteristic imaging findings and distinctive demographic and clinical factors help distinguish this disease from other osteonecrotic conditions, with which it can be confused. This report presents a rare, atypical case of bicondylar spontaneous osteonecrosis of the knee in a young patient, and highlights the importance of a clear understanding of the clinical and radiographic characteristics of this condition to accurately diagnose and treat it when evaluating osteonecrotic lesions of the knee., (Copyright 2009 Elsevier B.V. All rights reserved.)

Nitrogen-containing bisphosphonates such as zoledronic acid (ZOL) and pamidronate have been widely and successfully used for the treatment of cancer patients with bone metastases and/or hypercalcemia. Accumulating recent reports have shown that cancer patients who have received these bisphosphonates occasionally manifest bisphosphonate-related osteonecrosis of the jaw (BRONJ) following dental treatments, including tooth extraction. However, little is known about the pathogenesis of BRONJ to date. Here, to understand the underlying pathogenesis of BRONJ, we examined the effects of ZOL on wound healing of the tooth extraction socket using a mouse tooth extraction model. Histomorphometrical analysis revealed that the amount of new bone and the numbers of blood vessels in the socket were significantly decreased in ZOL-treated mice compared to control mice. Consistent with these results, ZOL significantly inhibited angiogenesis induced by vascular endothelial growth factor in vivo and the proliferation of endothelial cells in culture in a dose-dependent manner. In contrast, etidronate, a non-nitrogen-containing bisphosphonate, showed no effects on osteogenesis and angiogenesis in the socket. ZOL also suppressed the migration of oral epithelial cells, which is a crucial step for tooth socket closure. In addition, ZOL promoted the adherence of Streptococcus mutans to hydroxyapatite and the proliferation of oral bacteria obtained from healthy individuals, suggesting that ZOL may increase the bacterial infection. In conclusion, our data suggest that ZOL delays wound healing of the tooth extraction socket by inhibiting osteogenesis and angiogenesis. Our data also suggest that ZOL alters oral bacterial behaviors. These actions of ZOL may be relevant to the pathogenesis of BRONJ.

Traditionally, it is believed that structural failure of the ischemic epiphysis as well as changes in radiodensity seen in the early stage of Legg-Calvé-Perthes disease is due to the repair process. However, little is known if matrix properties are altered following ischemic injury of the juvenile femoral head. The purpose of this study was to determine the matrix mineralization density, an important determinant of material quality and strength, of the proximal femoral epiphysis in an experimental animal model of Perthes disease. Ten piglets were surgically induced with femoral head ischemia and euthanized at 4 and 8 weeks following surgery. Contralateral, unoperated femoral heads were used as controls. Bone and calcified cartilage mineralization density distribution parameters were determined using quantitative backscattered electron imaging (qBEI) in the epiphyseal calcified articular cartilage, subchondral bone and central trabecular bone region. Histological as well as radiographic assessment was also performed. In the necrotic calcified epiphyseal cartilage matrix, a significant increase in the mean degree of mineralization (CaMean: +24%, p<0.0001) as well as the homogeneity of mineralization (CaWidth: -21%, p<0.05) and a significantly reduced amount of low mineralized matrix (CaLow: -49%, p<0.0001) were already present at 4 weeks post-ischemia induction. Similar changes, but more moderate, were also seen in the subchondral bone region. In contrast, in the necrotic central trabecular region, significant changes in matrix mineralization were found at 8 weeks (CaMean: +4%, p<0.05; CaWidth: -22%, p<0.05; CaLow: -8%, p<0.05) but not at 4 weeks post-ischemia induction. Our findings indicate that the process of matrix mineralization continues in necrotic calcified articular cartilage and bone following femoral head ischemia, which leads to a higher and more homogenous mineralized tissue matrix altering its intrinsic material properties. This may also explain the increased radiodensity seen in the early stage of Perthes disease prior to the initiation of the repair process., ((c) 2009 Elsevier Inc. All rights reserved.)

Elastic flexible internal fixation stabilizes the fracture using the principle of splinting. Foregoing absolute stability using compression serves to maintain the mechano-biological induction of fracture healing. It also serves to maintain the blood supply to soft tissues and bone. The healing pattern seen after flexible fixation corresponds to that of secondary bone healing. It starts early and requires less precision, which in turn helps to avoid iatrogenic damage during reduction and stabilization.Prognosis based alone on the degree of fracture mobility is inadequate because spontaneous healing can be observed in wild animals even with great mobility while in turn minimal instability of closely reduced fractures may result in delayed or non-union. The determining factor for tissue differentiation is not mobility but deformation (strain) of the repair tissue. While tissue strain depends on mobility, it depends even more so - and is all too often disregarded - on the distance between the moving fracture surfaces. Strain plays an important role when choosing the method of immobilisation and predicting an outcome, determining the induction and tolerance of the repair tissue.

The World Health Organization predicts that people aged older than 65 years will comprise 20% of the world's population by 2030. One of the most commonly prescribed medications for the elderly are the bisphosphonates, which have been shown to significantly reduce debilitating and fatal fractures by preserving bone density and consequently saving governments billions of dollars annually. Despite rigorous testing, 190 million prescriptions worldwide and US$8000 million in revenue, there is a serious adverse effect called bisphosphonate-related osteonecrosis of the jaw, which is poorly described and difficult to treat. The difficulty is compounded by the inability of medical personnel to recognize and adequately refer these patients or take adequate precautions before instituting bisphosphonate therapy. A myriad of differentials and a lack of consensus on how to definitively treat these patients have made this new presentation a worrying precursor for millions of other consumers who will reach the 5-year oral half life of bisphosphonates, which is when they generally start to present. In this paper, we explore historical parallels and provide the most comprehensive review to date in the literature about the presentation, diagnosis, treatment, pathophysiology, oncogenic associations, and best practice guidelines. Legal action pursuant to bisphosphonate-related osteonecrosis of the jaw is underway on 3 continents, and we believe that every health care professional should become au fait with this condition for which our growing case series represents merely the tip of the iceberg.

Traumatic and overuse injuries of the hand and wrist are common in athletes. Increasingly, MR imaging is being used to complement clinical and radiographic assessment in the diagnosis and management of these injuries. MR imaging is able to image accurately the bones, tendons, ligaments, nerves, and other small structures of the hand and wrist. This article provides an overview of traumatic and overuse injuries of the hand and wrist in athletes and a review of the MR imaging appearances.

Objective: To examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid-associated osteonecrotic lesions in rabbits., Methods: Steroid-associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated., Results: Lesion formation without repair was observed at 2 weeks after induction of steroid-associated osteonecrosis. Rabbits displaying destructive repair (DR+) and those displaying reparative osteogenesis (DR-) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR+ rabbits compared with DR- rabbits, whereas the permeability index was significantly higher in DR+ rabbits compared with DR- rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR+ rabbits than in DR- rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR+ rabbits, whereas VEGF expression decreased in DR- rabbits from week 2 to week 6., Conclusion: Continuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously low- level MSCP and uncontrolled VEGF expression during inadequate repair of steroid-associated osteonecrotic lesions.

One of the most feared complications of long-term corticosteroid therapy is osteonecrosis (avascular necrosis, aseptic necrosis). There is, no doubt, a causal role for systemic corticosteroids inducing osteonecrosis with such chronic therapy. The controversy involves whether short-term (<1 month) courses of systemic corticosteroids can truly induce osteonecrosis. This article presents both the biologic basis and statistical support for why such short-term courses of systemic corticosteroids rarely, if ever, truly induce osteonecrosis. Data from two very large populations (renal transplantation and systemic lupus erythematosus) with overall increased risk for osteonecrosis are carefully examined in view of the aforementioned controversy.

Purpose: We hypothesized that radial shortening osteotomy (radial shortening) for skeletally immature patients with Kienböck's disease would induce overgrowth of the radius. The purpose of this study was to determine the effect of radial shortening on radial growth in skeletally immature patients with Kienböck's disease and to clarify the relationship between the postoperative growth alterations and the clinical results., Methods: Eight wrists of 8 skeletally immature patients with Kienböck's disease were treated with radial shortening. There were 3 boys and 5 girls, ranging in age from 11 to 18 (mean, 14) years old. All patients presented with open physis and negative ulnar variance. The length of the radial shortening equaled the amount of negative ulnar variance. Clinical assessment was based on the modified Nakamura scoring system. Radiographic assessment, including Lichtman's stages, ulnar variance, carpal height ratio, radial inclination, and volar tilt, was performed before surgery, immediately after surgery, and at follow-up. A difference in ulnar variance of more than 2 mm between these 3 measurements was considered to be overgrowth. Statistical comparisons were performed using paired t-tests., Results: At a mean follow-up period of 69 months, the mean clinical score was 19.7 of 21 maximum points, with all wrists rated as excellent. Radiographically, no progression of Lichtman stage was found in any patient. At follow-up, the x-ray and magnetic resonance imaging findings indicated lunate revascularization in all patients. Four of the 8 had overgrowth in the operated radius. On the other hand, other radiographic parameters showed no significant changes at follow-up. The occurrence of postoperative radial overgrowth did not notably affect the clinical scores., Conclusions: The current results suggest the probability of overgrowth of the radius in skeletally immature patients with Kienböck's disease treated with radial shortening. The postoperative radial overgrowth after this osteotomy had no effect on clinical and other radiographic outcomes., Type of Study/level of Evidence: Therapeutic IV.

Purpose of Review: Osteoporosis treatments will be used with increasing frequency as the population ages; however, relatively little is known about their long-term safety. Recent case reports cite a range of potential adverse events. We review data regarding atrial fibrillation, bone pain, osteonecrosis of the jaw (ONJ), atypical fractures, and osteosarcoma., Recent Findings: Incidence of bisphosphonate-related ONJ in osteoporosis patients is unclear, but several studies suggest rates may be higher than one in 100,000. Severe bone pain and esophageal cancer have been described among bisphosphonate users, but their relationship has not been carefully studied. The relationship between atrial fibrillation and bisphosphonates is unclear based on existing data, but the Food and Drug Administration's (FDA) analyses suggest no clear association. Although several case series discuss atypical fractures associated with bisphosphonate use, one epidemiologic study found no association. Finally, one case of osteosarcoma has been reported in a woman using teriparatide. One case in over 200,000 users suggests no increase in risk beyond background risk, but further evaluation is necessary., Summary: Although case reports of adverse events with osteoporosis medications suggest potential links, epidemiological analyses have largely failed to illuminate a strong, clear link between osteoporosis therapies and many adverse events, with ONJ an exception. Until further data are available, providers should be aware of these potential side effects, and inform their patients accordingly.

Core decompression of the humeral head has previously been used as a joint-preserving procedure for treatment of symptomatic osteonecrosis of the shoulder. In this article, we describe a new decompression technique, which involves multiple small-diameter (3-mm) percutaneous perforations. In our study population (early-stage disease), shoulder arthroplasty was avoided in all 15 patients (26 shoulders) for a mean follow-up of 32 months (range, 24-41 months). Of the 26 shoulders, 25 had successful clinical and functional outcomes (University of California Los Angeles shoulder score, >24 points), and 1 showed radiographic progression of the disease but has not needed further operative treatment. We compared our decompression results with those of a nonoperative historical control group, identified through a literature search. There was a 48% (143/299) rate of progression to arthroplasty in the control group at a follow-up ranging from 2 to 4.5 years. This outpatient, percutaneous perforations technique appears to be a low-morbidity method for relieving symptoms and deferring shoulder arthroplasty in patients with symptomatic osteonecrosis of the humeral head.

Bisphosphonates (BP) are the current standard of care for preventing malignant skeletal related-events. Recent reports have documented the relationship between osteonecrosis of the jaws (ONJ) and the use of BPs. Based on the opinion of experts, the purpose of our analysis was to summarize current knowledge, to propose therapeutic options, and to define areas of research. Identified risk factors were long-lasting exposure to BPs, intravenous nitrogen-containing BPs, and poor dental status. Three major hypotheses could explain the genesis of ONJ: excess of bone turnover inhibition, antiangiogenic effect, and local infection. Before the onset of therapy, the dental status must be controlled, and followed during treatment. Dental procedures could worsen the risk of ONJ, and indications must be well evaluated. When an ONJ occurs, the management should be adapted according to its extent. Thereby, a customization of BP therapy should be applied taking into account the aggressiveness of the underlying disease.

Study Question: Pathologic bone fractures in cryosurgery of bone tumors have been described in literature. This study utilizing a sheep model should prove the possible reduction of potential fracture while using a new miniature cryoprobe minimizing tissue damage and providing accurate control of the ablation process. Furthermore, postoperative histological changes should be investigated and the results correlated with the stability trials., Methods: In 24 sheep, ablation of the femur and the tibial bone on one side was carried out. Ablation of the right femur was limited to an area of 2 cm(2) with single cortical bone, whereas at the left tibia the whole proximal tibial plateau was included. The other side served as a control entity without cryoablation. After a period of 2, 4, and 6 months postoperative investigation of bending resistance of the femoral bone and of compression resistance of the tibial bone as well as histological findings were done in eight animals each., Results: After 2 months there was a significant difference (P < 0.05) regarding compression resistance between the treated and the contralateral tibia, whereas the bending resistance in the treated femur was slightly lower than on the contralateral side. After 4 and 6 months the cryo-treated part showed a tendency towards weakness. Histological findings showed bone necrosis with slight beginning repair after 2 months. Four and six months later, bone necrosis still existed with increasing development of woven bone and conversion into lamellar bone., Discussion: A thorough control of the freezing process and the low iatrogenous weakening of the bone due to placing the probe when modern miniature cryoprobes are used can minimize the risk of pathological postoperative fractures. However, at least 2 months after operation there is histological proof of bone healing with appropriate reduction of bone stability, which should be considered for the clinical application of this new technique.

The long-term success of total knee replacement is multifactorial, including factors relating to the patient, the operation and the implant. The purpose of this study was to examine the 20-year survival of the cemented Anatomical Graduated Component (AGC) total knee replacement. Between 1983 and 2004, 7760 of these were carried out at our institution. Of these, 6726 knees which received the non-modular metal-backed tibial component with compression-moulded polyethylene and had a minimum two-year follow-up were available for study. In all, 36 knees were followed over 20 years with a survival of the tibial and femoral components together of 97.8% (95% confidence interval (CI) 0.9851 to 0.9677), with no implants being revised for polyethylene wear or osteolysis. Age > 70 was associated with increased survival (99.6%, 95% CI 99.0 to 99.8) (p < 0.0001) but pre-operative valgus alignment reduced survival (95.1%, 95% CI 90.0 to 97.6) (p = 0.0056). Age < 55 (p = 0.129), pre-operative varus alignment (p = 0.707), osteonecrosis (p = 0.06), rheumatoid arthritis (p = 0.247), and gender (p = 0.666) were not statistically associated with failure. We attribute the success of the AGC implant to its relatively unconstrained articular geometry and the durability of a non-modular metal-backed tibial component with compression moulded polyethylene.