Bone marrow is an environment rich in its diversity of cell types and niches. Both hematopoietic and osteogenic stromal cells are present and have been studied extensively. Less is known about the function of one of the most abundant cell types in the bone marrow: adipocytes. There are several hypotheses that have been proposed including: passive role as a space filler; active role in the body's general lipid metabolism; role in providing a localized energy reservoir for emergency situations affecting the bone or hematopoiesis; support of differentiation or function of other cell types (such as bone, endothelial, and other stromal cells).

There are several human pathologies associated with increases in adipocyte hypertrophy or proliferation including changes associated with aging, osteoporosis, and osteonecrosis. The reasons for these changes are poorly understood. One etiology associated with both osteoporosis and osteonecrosis, corticosteroid therapy, has been shown to increase the lipid content of osteoblasts and adipocytes.

With osteonecrosis, several pathogenetic mechanisms involving adipocytes have been proposed:

Mechanical - increased size and number cause increased intraosseous pressure and decreased venous outflow

The possibility that adipocytes may actually play an active role in propagating specific pathologic features has only recently been discussed. This is in part due to our increasing understanding that adipocytes have an endocrine role in metabolism.

Only recently have scientists tried to identify specific cellular mechanisms that may be involved in the pathogenesis of osteonecrosis. Results from these studies will not only contribute to our understanding of the disease of osteonecrosis (and other diseases such as osteoporosis) but will also help us to appreciate the multiple functionalities of the heretofore unappreciated adipocyte.

Core decompression is a common treatment for early stage osteonecrosis of the femoral head due to the simplicity of the procedure and the positive results of this intervention. A number of different core decompression methods exist: including methods backfilled by a bone graft material and those without filling. Due to the inherent desire that the core decompression defect regenerate healthy bone, reduce pain, and stave off the need for total hip arthroplasty for some period of time, this surgically created defect is an excellent application for the use of a bone graft substitute.

Recently, an injectable calcium sulfate (CaSO₄)/calcium phosphate (CaPO₄) composite graft has become available for use in the treatment of surgically created defects. The synthetic graft is an injectable composite of CaSO₄, tricalcium phosphate (TCP) granules, and brushite that hardens in situ. The triphasic resorption pattern exhibited by this material in vitro and in pre-clinical canine studies has indicated that the CaSO₄ matrix resorbs at early time points to reveal a longer resorbing CaPO₄ scaffold for bone onlay. In a canine proximal humerus model, the use of this material in a critical bone defect has demonstrated a regenerate with higher compressive strength at 13 week time points than defects treated with CaSO₄ alone, defects treated with autograft, and normal untreated bone. By 26 weeks, the regenerated bone within the defect resembled normal bony architecture with similar mechanical properties.

Early clinical series have indicated similar results to the canine studies. Reports of early clinical findings have included a 12 patient benign bone tumor series with 4–12 month follow up and a core decompression series of 38 Ficat stage I–III hips with 6–16 month follow up. Preliminary radiological results in the bone tumor series showed peripheral resorption of the injectable CaSO₄/CaPO₄ composite with new bone formation along the resorbing edge. Clinically, patients in the bone cyst series have not experienced fractures or additional surgery and all patients have displayed full functional recovery. In the core decompression series, 32 of the 38 hips experienced pain relief and within the subset of 30 symptomatic hips, 24 had pain relief. These results, although preliminary, are promising outcomes.

Collectively, the pre-clinical and preliminary clinical results indicate that the use of an injectable CaSO₄/CaPO₄ composite could prove to be of benefit in core decompression of the femoral head. The staged resorption and dense bone formation evidenced in canine studies would be desirable in core decompression techniques where healthy bony ingrowth is the goal. Due to the straightforward compilation and use of this composite, the incorporation of this material as a backfill matrix into the core decompression procedure is technically simple. Although additional studies are certainly merited, these early clinical results are encouraging.

The Johns Hopkins University Department of Orthopaedics at the Good Samaritan Hospital, Baltimore, Maryland USA

Introduction: Historically, bone scintigraphy has been advocated as a useful diagnostic tool for patients with suspected osteonecrosis or in screening for multifocal disease. The principle aim of this study was to evaluate the sensitivity of bone scanning relative to magnetic resonance imaging in the diagnosis of osteonecrosis.

Methods: Forty-eight patients presented with suspected osteonecrosis of the shoulder, hip, knee, or ankle. All patients underwent simultaneous (less than three months apart) bone scans and magnetic resonance imaging studies as part of a diagnostic work-up. Histological confirmation of osteonecrosis was obtained for all suspected lesions in the study. The diagnostic yield for each imaging modality was then assessed and compared.

Results: All one hundred sixty-three (100%) histologically confirmed lesions were identified by magnetic resonance imaging, while only ninety-one lesions (56%) were identified by bone scan. There was complete uniformity of bone scans with magnetic resonance images in only 38% of patients (eighteen of forty-eight). Bone scanning identified 72% of lesions (forty-seven of sixty-five) in oligofocal patients (less than two involved joints) compared with 45% of the lesions (forty-four of ninety-eight) in multifocal patients (more than two joints involved). Sensitivity of the lesions was highest for the knee and hip and lower for the shoulder and ankle. Larger and later stage lesions had higher bone scan sensitivity.

Conclusions: The results of this study have demonstrated the low sensitivity of bone scintigraphy for diagnosing symptomatic osteonecrosis. Bone scanning did not detect 44% of the lesions (seventy-two of one hundred sixty-three). This study does not support the use of bone scans as a diagnostic or screening tool for this disease.

Introduction: Cementless total hip arthroplasty has been advocated for osteonecrosis of the femoral head (ONFH) as these patients are generally younger and more active than patients with osteoarthritis (OA). Since introduced in the early 1980’s, there have been several generations of cementless total hip prostheses. This study examined the outcome of the femoral stem of four generations of uncemented total hip prostheses.

Materials and Methods: One hundred and fifty-eight hips in 135 osteonecrosis patients (71 men, 64 women) who had a mean age of 46 years (range, 17 to 83) were included. The total number of prostheses included: PCA™ (77), E Series™ (47), Meridian™ (18), and Citation™ (16) (all Stryker, Mahwah, New Jersey). The mean follow-up was 105.5 +/− 60.8 months (range, 20 to 257 months). As part of an ongoing IRB-approved study, data collected includes Harris Hip (HHS) and QOL scores, re-operations (including revisions), and complications.

Results: The femoral components of 142 cases were not revised. These patients had a mean HHS of 86.3 +/− 13.2 points. Of the 15 revisions (9.6%), the primary reasons were loosening and/or significant osteolysis, but there was one infection and one chronic dislocation. The revisions included 10 PCA™ (13.0%) with a mean time to revision of 85 months (range, 25 to 132); 2 E Series™ (4.3%) with a mean time to revision of 85 months (2 cases in one patient; 68 and 101 months); 2 Meridian™ (11.1%) with a mean time to revision of 193 months (2 cases; 98 and 107 months); and 1 Citation™ (6.3%) with a time to revision of 30 months. The pooled revision rate of the 2^nd, 3rd, and 4^th generation was 5 of 80 (6.3%).

Discussion: There were no significant difference in revision rates between the different generations of uncemented femoral components (Chi Square, p=.433). However, the revision rates for the later generations were lower than the earlier generations.

Introduction: In the evaluation of various treatments that may have an effect on bone, there are certain inherent difficulties in selecting an appropriate outcome measure to determine whether a specific treatment is efficacious. This is particularly true for clinical studies.

Methods: Using Pubmed, a service of the U.S. National Library of Medicine that searches MEDLINE and other life science journals for citations of biomedical articles, a review of the current instruments used for outcome measures relating to osteonecrosis and bone blood flow was conducted. Abstracts from previous ARCO meetings were also reviewed.

Results: For the treatment of osteonecrosis, most outcome measures have focused on pain relief, surgery or need for surgery, disease progression (advancing stage), and change in lesion size. The first three options may be influenced by investigator bias and knowledge/experience. The last option may also be influenced by the technique used.

Imaging techniques continue to gain in sophistication. Gd-enhanced MRI can be used to assess perfusion of the diseased tissue. Doppler ultrasonography has also been used to estimate blood flow noninvasively. Near Infrared Spectroscopy (NIRS) can be used to measure tissue oxygenation.

While there has been recent interest in using biomarkers or genetic markers in the diagnosis and analysis of disease progression, more research is needed to determine the sensitivity and specificity of these techniques with respect to osteonecrosis.

Conclusion: Although there are a number of tests that can be used to evaluate the effect of a specific treatment on osteonecrosis, the definitive assessment will likely remain whether the disease progresses to the point that major surgery (resurfacing, vascularized fibular grafting, total joint replacement, e.g.) is required to relieve pain and restore function.

Introduction: The response of osteoblasts to dexamethasone is dose-dependent. While low doses are used to stimulate osteoblasts to maintain their phenotype, high doses are cytotoxic. The purpose of this study was to test the hypothesis that mechanical stimulation alters the response of osteoblast-like cells to dexamethasone.

Materials & Methods: MG-63 cells were propagated on 6-well Flexcell plates (flexible silicone membranes) under standard culture conditions. One half of the plates were subjected to biaxial strain at a frequency of 0.5 Hz through an imposed vacuum pressure of -7kPa (~1% stretch; 0.01 strain) for 42 hours using the Flexercell Apparatus. Replicate samples were maintained under static conditions. Simultaneously, the cells were exposed to either 0, .001, .01, or .1 nM of dexamethasone. The wells were then spiked with tritiated thymidine for 6 hours. The results were normalized to the control values. Triplicate wells were included for each experimental condition; and the experiment was repeated four times. Data were analyzed by JMP statistical package (SAS).

Results: Increasing doses of dexamethasone resulted in decreasing cellular proliferation. For the unflexed cells, we noted the following reduction in proliferative capacity: 0.86% ± 0.09 (.001nM), 0.50% ± 0.07 (.01nM), and 0.39% ± 0.07 (.1nM). Similar results were observed for the cells exposed to cyclic loading: 0.89% ± 0.12 (.001nM), 0.52% ± 0.08 (.01nM), and 0.47% ± 0.07 (.1nM).

Discussion: Our results confirmed the work of others that there is a decrease in the proliferation of osteoblasts (incubated under static conditions) when exposed to high levels of dexamethasone. Although cyclic loading had no effect on the proliferative response of osteoblasts to dexamethasone, it may still have had an effect on cellular metabolism or function, which remains to be evaluated.

Introduction: Multiple classification systems for avascular necrosis of the hip have been developed to assist physicians in the diagnosis and treatment of this potentially debilitating disorder. However, this lack of consistency makes clinical decision making difficult when comparing publications. The purpose of this study was to quantify the classification systems reported since 1985 (post-MRI) and identify consistent factors which would allow cross-publication comparisons to be made.

Materials and Methods: The authors performed a PubMed search for reports of outcome studies concerning treatment methods of hip avascular necrosis that were the initial basis for analysis. All studies reported since 1985 were included in the analysis if outcomes of greater than 10 patients treated for this disease were reported. Classification systems utilizing at least one factor were also identified. Tabulation of how frequently these classification systems were used in terms of the number of studies reporting results was performed.

Results: Fifteen major classification systems utilizing more than one radiographic factor were identified with 9 having one to three modifications reported throughout the literature. Additionally, 14 systems utilized either MRI or anatomic factors. Cross-publication analysis revealed five major classification systems which were utilized in greater than 80% of the reported studies.

Discussion: This analysis of the reported classification systems for avascular necrosis of the femoral head revealed several similarities between systems. A cross system analysis can be made if data is collected according to patient symptoms, magnetic resonance imaging findings, and x-ray findings which would allow for the use of any staging system.

Introduction: Evidence-based medicine is a form of practice in which the physician accesses relevant, state-of-the-art research findings to guide the care of the individual patient (Gordon and Cameron, 2000). Therefore, evidence-based medicine should influence the decision making process when developing a treatment algorithm for early stage osteonecrosis. It was the purpose of this project to explore the literature concerning surgical options that are used currently to treat early stage osteonecrosis.

Materials and Methods: Literature searches were conducted using PubMed (National Library of Medicine, USA) to identify journal articles pertaining to the treatment of pre-arthrosis osteonecrosis during the past decade. The articles were screened to include only those with greater than 5 patients and greater than two year follow-up.

Results: Published reports in medical journals included: core decompression with and without nonvascular grafting (18); core decompression augmented with BMP or bone marrow cells (2); bone cement (1); vascularized graft – fibular or iliac (10); osteotomy (26); osteotomy and vascularized grafts (3); trap-door procedure (2); and hemiarthroplasty/resurfacing arthroplasty (9). There was one review of nonoperative treatment, but no clinical studies. There were only a few case reports concerning osteochondral graft/osteochondroplasty; which did not meet the inclusion criteria. Several classification systems were used: Ficat and Arlet (55%); University of Pennsylvania / Steinberg (21%); Japanese Investigational Committee (13%); Marcus (2%); Myers (3%); ARCO (5%), and other (1%). A majority of reports included follow-up of 5 years or greater (91%). Most studies (91%) were not randomized, control-matched, or prospective.

Discussion: Several surgical options are available for the treatment of pre-arthrosis osteonecrosis. However, it is not possible to apply evidence-based medicine practices to the research relating to the treatment of osteonecrosis as most of the research is not controlled and not comparative. This represents a substantial void in our knowledge base concerning osteonecrosis which remains to be filled.

Introduction: In a previous study (ARCO, 2002), we reported that the clinical results of revision total hip arthroplasty for osteonecrosis patients were less satisfactory than those found for a matched group of osteoarthritis patients. The aim of this study was to evaluate the potential factors that may have contributed to these findings.

Materials and Methods: This study included 34 hips in 30 osteonecrosis patients who had undergone revision of a femoral total hip arthroplasty component. There were 19 men (22 hips) and 11 women (12 hips) who had a mean age of 46.1 years (range, 28 to 69 years). The surgeries were performed between March 1984 and January 2001. Most femoral stems (91%) were implanted without cement. Prostheses were of different stem lengths, but most (97%) were proximally porous-coated. The mean follow-up was 8.2 years [range, 0.1 (a re-revision) to 19.8 years]. A physical examination as well as patient and physician outcome forms were collected at each visit. Preoperative x-rays were categorized according to the technique of Della Valle and Paprosky. A Kaplan-Meier survival analysis was performed (PEPI statistical software package).

Results: Risk factors for osteonecrosis included 15 corticosteroid, 8 alcohol, 7 trauma, and 4 unknown. This was the first revision in 27 cases, second revision in 5 cases, and third revision in 2 cases. Preoperatively, the defects included 4 Type I, 9 Type II, 15 Type IIIA, 2 Type IIIB, 1 Type IV, and 3 unknown types. Of the 34 hips, the femoral component was re-revised in 12 cases. One of the failures was the only fully porous coated stem that was implanted. One of the 3 cemented implants failed, as compared to 11 of the 31 implanted without cement. Survival rates were 90.9% (74.4%–97.1%) at 5 years, 54.8% (24.9%–81.6%) at 10 years, 54.8% (19.9%–85.6%) at 15 years, and 27.4% (1.7%–88.9%) at 20 years. There was no relationship between frequency of re-revision and defect category, risk factors, or age.

Discussion: Although there was a high failure rate (12/34; 34%) in this patient cohort, over 50% survived at least 10–15 years. The lack of a relationship between the patient age or the extent of defect and re-revision suggest that other factors concerning this disease need to be examined.

Osteonecrosis (ON) of the femoral head is a condition that afflicts approximately 20 000 new patients per year, at an average age of 38. Twenty-five percent of the patients seen in our institution are under 25. Without treatment, most of these patients can be expected to need a total hip replacement (THR). However preservative procedures have a significant failure rate, and some, significant morbidity.

It is desirable to avoid or delay THR, because most of the patients with ON will outlive the prosthesis, at the current state of the art. There are four issues that need to be weighed to arrive at a reasonable algorithm for the preservative treatment of ON; patient risk factors, morbidity of the proposed procedure, size of the lesion, and stage of the lesion.

Risk – risk of outliving a THR. Age, sex, weight, general health, associated diseases, and level of activity all influence the longevity of a THR. The greater the risk, the greater the indication for a preservative procedure.

Morbidity – There is a big difference between core decompression and a complex osteotomy. The overall risk of the procedure and the impact on THR must be considered.

Size – Large lesions do much worse than small lesions at any stage.

Stage – Pre-collapse lesions do better than post-collapse lesions.

Using the above issues might lead the surgeon to do a THR on a 25-year old with a large post-collapse lesion or a core decompression on a 60-year old with a small symptomatic pre-collapse lesion. All of the issues must be considered to make sense out of a complex clinical situation.

Many of our most important pharmaceuticals have their origins in plants, such as digoxin, penicillin and coumadin. However, many physicians are deeply sceptical about the use of natural remedies. This scepticism is based on the concerns about patient self-diagnosis and treatment as well as the lack of scientific testing of claims. Nonetheless, a new class has emerged called nutraceuticals – nutritional supplements with pharmaceutical properties. Because these substances are relatively unregulated, there is no requirement for rigorous scientific testing prior to marketing. This lack of regulation also poses problems with purity and quality control. Even so, patients are being bombarded with, and responding to, claims of the results of these of herbs, nutraceuticals, and nutritional supplements.

Glucosamine and chondroitin sulfate sales alone in the USA are estimated at $600 million. Sales of all neutraceuticals and vitamin supplements in the USA exceeded $12 billion in 1999. Many physicians took offence at the title of the book by Theodaskis et al., The Arthritis Cure, because they know no cure exists. Patients, on the other hand, pushed sales of the book to the best-seller list. Moreover, glucosamine and chondroitin have been widely studied in tissue culture, animal models of arthritis, veterinary clinical trials, and human comparative or placebo controlled trials. No published study has failed to show a positive effect and no trial has shown significant side affects. These nutraceuticals have become our first line of treatment for osteoarthritis.