Clinical Orthopaedics and Related Research ®

A Publication of The Association of Bone and Joint Surgeons ®

Symposium: Molecular and Surgical Advances in Osteonecrosis 19 articles


F-18 Fluoride Positron Emission Tomography of the Hip for Osteonecrosis

Vinod Dasa MD, Hani Adbel-Nabi MD, PhD, Mark J. Anders MD, William M. Mihalko MD, PhD Osteonecrosis (ON) of the femoral head continues to be a devastating disorder for young patients. We evaluated the F-18 fluoride positron emission tomography (PET) imaging modality for use in detection of the bone involved in ON of the hip. We retrospectively reviewed the records of 60 consecutive patients diagnosed with ON and interviewed all by phone. Eleven patients (17 hips) of those interviewed agreed to participate in the study. We classified the ON using the University of Pennsylvania classification system and compared each patient’s plain AP bone scan, single photon emission 3-D computed tomography, and MRI. ON was associated with HIV, alcohol, steroid use, and polycythemia vera in this group. Nine of 17 hips (8 patients) had acetabular increased uptake when using the F-18 fluoride PET scans that were not seen on MRI, single photon emission computed tomography, or bone scans. These data suggest earlier acetabular changes in osteonecrosis may exist that traditional imaging modalities do not reveal.,[object Object]

Nonvascularized Bone Grafting Defers Joint Arthroplasty in Hip Osteonecrosis

Thorsten M. Seyler MD, David R. Marker BS, Slif D. Ulrich MD, Tobias Fatscher BS, Michael A. Mont MD A variety of nonvascularized bone grafting techniques have been proposed with varying degrees of success as treatment alternatives for osteonecrosis of the femoral head. The success of these procedures may be enhanced using ancillary growth and differentiation factors. We retrospectively reviewed 33 patients (39 hips) with osteonecrosis of the hip who had nonvascularized bone grafting procedures with supplemental OP-1. We compared the outcomes in this cohort to similar patients treated nonoperatively or with other nonvascularized bone grafting procedures. We used a trapdoor to make a window at the head-neck junction to remove necrotic bone and packed the excavated area with autogenous cancellous bone graft, marrow, and OP-1. The minimum followup was 24 months (mean, 36 months; range, 24–50 months). We performed no further surgery in 25 of 30 small- and medium-sized lesions (80%) but did in two of nine large lesions. Hips with Ficat Stage II disease were not reoperated in 18 of 22 cases during the followup periods. Our short-term results compare similarly to nonoperative treatment and other reports of nonvascularized bone grafting. With the addition of ancillary growth factors, these procedures effectively reduce donor site morbidity and may defer joint arthroplasty in selected patients.,[object Object]

Long-term Followup of Vascularized Fibular Grafting for Femoral Head Necrosis

Myung-Chul Yoo MD, PhD, Kang-Il Kim MD, PhD, Chung-Soo Hahn MD, PhD, Javad Parvizi MD Vascularized fibular grafting has been used for treatment of osteonecrosis of the femoral head and although some reports demonstrate successful short- to mid-term outcomes, long-term results are still unknown. We retrospectively reviewed 135 patients (151 hips) who underwent vascularized fibular grafting for osteonecrosis of the femoral head. One-hundred and ten patients (124 hips) were followed for a minimum 10 years (mean, 13.9 years; range, 10–23.7 years). The mean Harris hip score improved from 72 to 88. At the latest followup, we found improved or unchanged radiographs in 37 of 59 hips initially Stage II hips and 39 of 65 Stage III hips. Thirteen hips (13 patients) (10.5%) failed treatment and underwent total hip arthroplasty. The location and size of the necrotic lesion and the patient’s age influenced long-term survival of the graft. Postoperative complications included clawing of the big toe in 17 patients, partial peroneal nerve palsy in two, and superficial infection in two. Subtrochanteric fracture occurred in two hips. The data suggest free vascularized fibular grafting was successful in maintaining joint function and delaying the need for joint replacement procedure. Graft survival was associated with the patient’s age and size and location of the lesion but not etiology and stages of the disease.,[object Object]

THA Using an Anatomic Stem in Patients With Femoral Head Osteonecrosis

Yong-Chan Ha MD, Hee Joong Kim MD, Shin-Yoon Kim MD, Tae-Young Kim MD, Kyung-Hoi Koo MD Treating young patients with femoral head osteonecrosis (ON) remains challenging. Anatomic stems were introduced in the 1980s and 1990s to improve the proximal canal fit in an attempt to enhance long-term implant survival, an important aspect of treating young patients. We began using one design in 1993 and asked three questions to confirm whether the design criteria improved outcomes in patients with ON: (1) What is the long term survivorship of these implants?; (2) What is the amount and rate of wear?; and (3) What is the incidence of osteolysis? We retrospectively reviewed 56 patients (69 hips) who underwent THA for femoral head ON with a cementless anatomic stem proximally coated with hydroxyapatite. Four patients (four hips) were lost to followup and 16 patients (19 hips) died. In the remaining 36 patients (46 hips) the minimum followup was 10 years (mean, 11.2 years; range, 10–13 years). The mean age at operation was 48.6 years. The average Harris hip score at last followup was 87 points. Worst-case survivorship was 58.1% at 13 years and best-case was 93.3%. The average linear wear of the polyethylene liner was 2.02 mm and the average annual wear was 0.18 mm per year. Thirty-seven hips (80%) had femoral osteolysis and 14 (30%) had acetabular osteolysis. One patient who had extensive femoral osteolysis and stem loosening was revised at 11.2 years postoperatively. The high rates of polyethylene wear and osteolysis are of concern.,[object Object]

Vascularized Fibular Grafting for Osteonecrosis of the Femoral Head With Unusual Indications

J. Mack Aldridge MD, James R. Urbaniak MD We retrospectively reviewed the charts of 154 patients of various subgroups treated with the free vascularized fibular graft procedure for osteonecrosis of the femoral head (ONFH), evaluating pre- and postoperative Harris hip scores, hip range of motion, radiographs, and number of conversions to total hip arthroplasty (THA). Patients were followed a minimum of 1 year (mean, 6.8 years, range, 1 to 19 years). Athletes and patients with pyarthrosis-related osteonecrosis had high Harris hip scores at final review with scores of 94 and 97, respectively. Patients with ONFH after a slipped capital femoral epiphysis or following pregnancy had a low conversion rate to THA at 6% and 8%, respectively. Twenty-five percent of patients with transplant-related osteonecrosis of the femoral head were converted to THA at an average of 2.7 years. However, with select subsets of patients (athletes, pregnancy, organ transplant, femoral neck non-union, slipped capital femoral epiphysis, infection) the FVFG can result in a high rate of success.,[object Object]

Transtrochanteric Posterior Rotational Osteotomy for Osteonecrosis

Yoichi Sugioka MD, PhD, Takuaki Yamamoto MD, PhD When osteonecrosis is located in the mid- to posterior region, we generally perform a transtrochanteric posterior rotational osteotomy. We retrospectively reviewed the clinical and radiographic results in 47 consecutive patients (51 hips) in whom we performed posterior rotational osteotomies. The average age was 37 years at the time of surgery. There were 30 male and 17 female patients. Thirty-six hips were ARCO Stage III, and 15 were Stage IV. Conversion to THA was defined as the failure end point. Three patients died and one was lost to followup. We were therefore able to follow 43 patients (46 of the 51 hips, or 90%) a minimum of 1.2 years (average, 12 years; range, 1.2–21 years). We used the Harris hip score for preoperative and most recent followup. The average preoperative Harris hip score of 52 points improved to an average of 84 at the latest followup. Radiographically, the osteonecrosis in 30 hips (65%) had no progressive collapse, and 13 (28%) showed osteoarthritic changes, but no patients underwent THA. A posterior rotational osteotomy appears useful for patients with extensive necrosis and advanced collapse.,[object Object]

Untreated Asymptomatic Hips in Patients With Osteonecrosis of the Femoral Head

Byung-Woo Min MD, Kwang-Soon Song MD, Chul-Hyun Cho MD, Sung-Moon Lee MD, Kyung-Jae Lee MD Because there is no consensus regarding the factors predicting femoral head collapse in asymptomatic osteonecrosis of the hip, we studied the risk factors for collapse. Between 1990 and 2000, we used MRI to confirm asymptomatic osteonecrosis of the femoral head in 81 patients (81 hips) whose other hip had nontraumatic symptomatic osteonecrosis and we monitored them prospectively. The minimum followup was 5 years (mean, 8.3 years; range, 5–16 years). At the latest followup, 31 hips (38%) were symptomatic and 26 hips (32%) had collapsed. The mean interval between diagnosis and collapse was 4.1 years. We observed no correlation between femoral head collapse and patients’ age, gender, weight, presumed cause of osteonecrosis, or length of followup. With combined factors, only extent of large necrotic lesion (hazard ratio, 4.06; 95% confidence interval, 1.29–12.77) and location of Type C2 necrotic lesion (hazard ratio, 6.35; 95% confidence interval, 1.18–34.11) predicted collapse.,[object Object]

Pitavastatin may Reduce Risk of Steroid-induced Osteonecrosis in Rabbits: A Preliminary Histological Study

Kenjiro Nishida MD, Takuaki Yamamoto MD, PhD, Goro Motomura MD, PhD, Seiya Jingushi MD, PhD, Yukihide Iwamoto MD, PhD Several animal and human studies suggest pharmacological approaches may prevent steroid-induced osteonecrosis (ON). We asked whether the newly developed 3-hydroxymethyl-3-glutaryl-CoA (HMG-CoA) reductase inhibitor, pitavastatin, could prevent steroid-induced ON in rabbits. We injected 65 adult male Japanese white rabbits once with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. The rabbits were divided into two groups; one group of 35 rabbits received pitavastatins (PS), and the other group of 30 rabbits received no prophylaxis (CTR). Hematological examinations were performed just before the steroid injection (0 weeks) and at 1 and 2 weeks after steroid injection; both the femora and the humeri were histologically examined 2 weeks postinjection. The incidence of histologic changes consistent with early ON in the PS group (13 of 35; 37%) was lower in comparison to the CTR group (21 of 30; 70%). The size of the bone marrow fat cells in the PS group (56.6 ± 10 μm) was smaller than those in the CTR group (60 ± 4 μm). The data suggest pitavastatin has the potential to lower the incidence of steroid-induced ON in rabbits.

Modified Transtrochanteric Rotational Osteotomy for Femoral Head Osteonecrosis

Taek Rim Yoon MD, Azlina Amir Abbas MD, Chang Ich Hur MD, Sang Gwon Cho MD, Jin Ho Lee MD Osteonecrosis of the femoral head is a disabling condition affecting young patients and treatment of the disease in these patients is variable. We retrospectively reviewed 39 patients (43 hips) in whom a modified transtrochanteric rotational osteotomy was performed for osteonecrosis. The minimum followup was 24 months (mean, 36.6 months; range, 24–52 months). The mean patient age was 34.3 years (range, 20–51 years). Based on the ARCO classification, 17 hips were classified as Stage II and 26 as Stage III. We performed rotational osteotomy alone in 15 cases, in combination with simple bone grafting in three, and in combination with muscle-pedicle-bone grafting in 25. Sixteen of 17 ARCO Stage II cases and 24 of 26 ARCO Stage III cases had no progression of collapse or lesion size; three hips progressively collapsed. Of the 40 hips without progression the Harris hip score improved from a mean 70 to 92 points at final followup, as did the range of motion of the hip. Modified transtrochanteric rotational osteotomy is an effective method for delaying the progression of collapse in the treatment of selected cases of osteonecrosis of the femoral head.,[object Object]

Do Modern Techniques Improve Core Decompression Outcomes for Hip Osteonecrosis?

David R. Marker BS, Thorsten M. Seyler MD, Slif D. Ulrich MD, Siddharth Srivastava BA, Michael A. Mont MD Core decompression procedures have been used in osteonecrosis of the femoral head to attempt to delay the joint destruction that may necessitate hip arthroplasty. The efficacy of core decompressions has been variable with many variations of technique described. To determine whether the efficacy of this procedure has improved during the last 15 years using modern techniques, we compared recently reported radiographic and clinical success rates to results of surgeries performed before 1992. Additionally, we evaluated the outcomes of our cohort of 52 patients (79 hips) who were treated with multiple small-diameter drillings. There was a decrease in the proportion of patients undergoing additional surgeries and an increase in radiographic success when comparing pre-1992 results to patients treated in the last 15 years. However, there were fewer Stage III hips in the more recent reports, suggesting that patient selection was an important reason for this improvement. The results of the small-diameter drilling cohort were similar to other recent reports. Patients who had small lesions and were Ficat Stage I had the best results with 79% showing no radiographic progression. Our study confirms core decompression is a safe and effective procedure for treating early stage femoral head osteonecrosis.,[object Object]

Electromagnetic Fields

Masashi Ishida MD, Mikihiro Fujioka MD, PhD, Kenji A. Takahashi MD, PhD, Yuji Arai MD, PhD, Toshikazu Kubo MD, PhD Establishing a means to prevent osteonecrosis after corticosteroid administration is an important theme. We asked whether pulsed electromagnetic field stimulation, a noninvasive treatment, could prevent osteonecrosis. Ninety rabbits were divided into four treatment groups: (1) exposure of 10 hours per day to electromagnetic stimulation for 1 week, followed by injection of methylprednisolone (20 mg/kg), and exposure of 10 hours per day to electromagnetism for a further 4 weeks (n = 40); (2) methylprednisolone injection only (n = 40); (3) no treatment (n = 5); and (4) exposure of 10 hours per day to electromagnetism for 5 weeks (n = 5). After 5 weeks, we harvested and histologically examined femurs bilaterally. The frequency of osteonecrosis was lower in the steroid-electromagnetism group (15/40) than in the steroid-only group (26/40). No necrotic lesions were found in the two control groups. We observed no clear effects of electromagnetism on the number, location, extent, and repair of necrotic lesions and intramedullary fat cell size in affected rabbits. Pulsed electromagnetic field stimulation reportedly augments angiogenesis factors and dilates blood vessels; these effects may lower the frequency of osteonecrosis. Exposure to pulsed electromagnetic field stimulation before corticosteroid administration could be an effective means to reduce the risk of osteonecrosis.

Metal-on-Metal Hip Arthroplasty Does Equally Well in Osteonecrosis and Osteoarthritis

Manish R. Dastane MD, William T. Long MD, Zhinian Wan MD, Lisa Chao BS, Lawrence D. Dorr MD Many previous reports suggest total hip arthroplasty performs suboptimally in young patients with osteonecrosis. We retrospectively compared the performance of metal-on-metal articulation in a select group of 107 patients with 112 hips (98 uncemented and 14 cemented stems) 60 years of age or younger with either osteonecrosis (27 patients, 30 hips) or primary osteoarthritis (80 patients, 82 hips). We evaluated all patients with patient-generated Harris hip score forms and serial radiographs. Five mechanical complications were caused by impingement, two with pain, two dislocations, and one liner dissociation. At a minimum followup of 2.2 years (mean, 5.5 years; range, 2.2–11.7 years), we observed no osteolysis or aseptic loosening in the osteonecrosis group, whereas one osteoarthritic hip had cup revision for loosening (none showed evidence of osteolysis). None of the stems were loose. Patients with osteonecrosis or primary osteoarthritis were similar in clinical and radiographic performance. The patients with metal-on-metal hip arthroplasty for osteonecrosis had no revisions for aseptic loosening, but did have one liner change in a cup for painful impingement.,[object Object]

Extent of Osteonecrosis on MRI Predicts Humeral Head Collapse

Takashi Sakai MD, PhD, Nobuhiko Sugano MD, PhD, Takashi Nishii MD, PhD, Takehito Hananouchi MD, Hideki Yoshikawa MD, PhD Although MRI is useful for predicting progression of osteonecrosis (ON) of the femoral head or femoral condyle, predicting outcome of atraumatic osteonecrosis of the humeral head using MRI has not been previously examined. We asked whether the prognosis was related to the extent and location of necrotic lesions on MRI. We investigated 46 radiographically noncollapsed humeral heads in 27 patients, 24 steroid-related and three alcohol-related, using MRI and serial radiographs. The minimum followup was 24 months (mean, 84.9 months; range, 24–166 months). The necrotic lesion was typically located at the medial and superior aspect of the humeral head. The necrotic angle, which expressed the extent of the necrotic lesion, was measured on midoblique-coronal plane (range; 0°–134.7°) and on midoblique-sagittal plane (range; 0°–150.6°). Of the 46 lesions, 34 were less than 90° and did not collapse, whereas 11 of the other 12 lesions of more than 90° (92%) collapsed within 4 years. Of these 11 collapsed lesions, four of less than 100° did not progress, followed by reparative reaction on plain radiographs, whereas the other seven of more than 100° progressed to osteoarthritis. The extent of a necrotic lesion on MRI is useful to predict collapse of the humeral head.,[object Object]

Preventive Effects of Puerarin on Alcohol-induced Osteonecrosis

Yisheng Wang MD, Li Yin MD, Yuebai Li PhD, Peilin Liu MD, Quanjun Cui MD Alcohol can induce adipogenesis by bone marrow stromal cells and may cause osteonecrosis of the femoral head. Currently, there are no medications available to prevent alcohol-induced osteonecrosis. We hypothesized puerarin, a Chinese herbal medicine with antioxidative and antithrombotic effects, can prevent alcohol-induced adipogenesis and osteonecrosis. Both bone marrow stromal cells (in vitro) and mice (in vivo) were treated either with ethanol or with ethanol and puerarin, with an untreated group serving as a control. In the in vitro study, the number of adipocytes, contents of triglycerides, and levels of PPARγ mRNA expression were decreased and alkaline phosphatase activity, contents of osteocalcin, and levels of osteocalcin mRNA expression were increased in cells treated with both alcohol and puerarin, compared with cells treated with alcohol only. In the in vivo study, marrow necrosis, fat cell hypertrophy and proliferation, thinner and sparse trabeculae, diminished hematopoiesis, and increased empty osteocyte lacunae in the subchondral region of the femoral head were observed in mice treated with alcohol. However, no such changes were seen in femoral heads of mice treated with alcohol and puerarin. The data suggest puerarin can inhibit adipogenic differentiation by bone marrow stromal cells both in vitro and in vivo and prevents alcohol-induced osteonecrosis in this model.

Ethanol May Suppress Wnt/β-catenin Signaling on Human Bone Marrow Stroma Cells

Ching-Hua Yeh MS, Je-Ken Chang MD, Yan-Hsiung Wang PhD, Mei-Ling Ho PhD, Gwo-Jaw Wang MD Ethanol and glucocorticoids are risk factors associated with osteonecrosis. Previous reports suggest ethanol and glucocorticoids induce adipogenesis, decrease osteogenesis in bone marrow stroma cells, and produce intracellular lipid deposits resulting in death of osteocytes. The Wnt/β-catenin signal pathway is involved in the regulation of homeostasis of bone and we presume glucocorticoids and ethanol may induce osteonecrosis in humans through a similar mechanism as in rodents. We hypothesized (1) ethanol, like glucocorticoids, decreases osteogenesis and increases adipogenesis through the Wnt/β-catenin signaling pathway in human bone marrow stromal cells; and (2) ethanol decreases intranuclear translocation of β-catenin. We found both dexamethasone and ethanol decrease the gene and protein expression of osteogenesis and increase that of adipogenesis through Wnt signaling-related genes by semiquantitative and quantitative polymerase chain reaction and Western blot. Ethanol hampered intranuclear translocation of β-catenin by immunofluorescence analysis. The data suggest the Wnt/β-catenin signaling pathway may be associated with ethanol-induced osteonecrosis.

Heritable Thrombophilia-Hypofibrinolysis and Osteonecrosis of the Femoral Head

Charles J. Glueck MD, Richard A. Freiberg MD, Ping Wang PhD We hypothesized that inherited thrombophilia and hypofibrinolysis were risk factors for osteonecrosis of the femoral head. We compared measures of thrombophilia and hypofibrinolysis in referred new adult patients with idiopathic osteonecrosis (n = 71) or secondary osteonecrosis (n = 62) with the same measures in sex- and race-matched healthy control subjects. Heritable thrombophilic Factor VIII and hypofibrinolytic Lp(a) were more frequently high in the 71 patients with idiopathic osteonecrosis than in control subjects. High Factor VIII, Factor V Leiden heterozygosity, and resistance to activated protein C, all heritable thrombophilias, were more frequently present in the 62 patients with secondary osteonecrosis than in control subjects. Our data suggest inherited thrombophilia and hypofibrinolysis are risk factors for both idiopathic and secondary osteonecrosis of the head of the femur.,[object Object]

Genetic Background of Nontraumatic Osteonecrosis of the Femoral Head in the Korean Population

Jun-Dong Chang MD, PhD, Mina Hur MD, PhD, Sang-Soo Lee MD, PhD, Je-Hyun Yoo MD, Kyu Man Lee MD, PhD Major thrombophilic mutations have been identified as risk factors for nontraumatic osteonecrosis of the femoral head (ONFH) in Caucasians. We asked whether the genetic background of patients with ONFH in the Korean population was similar. We analyzed factor V G1691A mutation (factor V Leiden), prothrombin G20210A mutation, and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in 71 patients (53 men, 18 women) with ONFH. We classified these patients as 51 alcohol-induced, 18 idiopathic, one steroid-induced, and one dysbaric. We recruited 200 normal control subjects (128 men, 72 women). We used multiplex PCR/restriction fragment length polymorphism for each genotyping. We observed neither factor V Leiden nor prothrombin G20210A mutation. Although methylenetetrahydrofolate reductase A1298C genotypes were not associated with osteonecrosis, methylenetetrahydrofolate reductase C677T variant genotypes increased the risk of ONFH compared with 677CC. Odds ratios of 677CT and 677CT+TT were 2.00 (95% confidence interval, 1.05–3.81) and 1.96 (95% confidence interval, 1.07–3.59), respectively, compared with 677CC. Our data suggest methylenetetrahydrofolate reductase C677T polymorphism plays a role in the pathogenesis of osteonecrosis in the Korean population. It also implies the genetic risk profile of ONFH may differ among ethnic populations.,[object Object]