Necrobiosis and T-lymphocyte infiltration in retrieved aseptically loosened metal-on-polyethylene arthroplasties.

BACKGROUND AND PURPOSE: Soft tissue necrobiosis and T-lymphocyte infiltration within the periprosthetic soft tissue have been linked to a suggested hypersensitivity reaction of the delayed-type following the metal-on-metal arthroplasty. While we observed both synovial necrobiosis and lymphocyte infiltrates in synovial tissues with failed metal-on-polyethylene prostheses, we hypothesized that both findings are unspecific for metal-on-metal bearing coupes. Thus, we wished to quantify the extent of necrobiosis and the amount of T-lymphocyte infiltration in aseptically loosened metal-on-polyethylene prostheses. MATERIALS AND METHODS: We analyzed 28 consecutive synovial biopsy specimens obtained at revision surgery of aseptically loosened metal-on-polyethylene prostheses (19 hips and 9 knees) and quantified both the extent of necrobiosis vertically and the density of CD3+, CD4+, and CD8+ lymphocytes within the joint capsular tissue. We excluded patients with inflammatory skeletal disease or with a history of metal hypersensitivity. RESULTS: We found necrobiosis in 23 of 28 cases and it was most often connected with the superficial portions of the synovium. Necrobiosis of deeper tissues was seen in 8 specimens and it was strongly associated with superficial necrobiosis. While CD3+ lymphocytes were detected in each biopsy, 4 cases with more than 300 CD3+ lymphocytes were identified in the group of 26 cases that presented with more than 100 CD3+ lymphocytes within one high-power field. 16 cases with more than 100 CD3+ lymphocytes also showed concomitant superficial necrobiosis of the synovium. In the inflammatory infiltration of periprosthetic synovium, CD8+ lymphocytes predominated over CD4+ cells. INTERPRETATION: Synovial necrobiosis and infiltration of T-lymphocytes are common findings in tissues around aseptically loosened metal-on-polyethylene arthroplasty in patients without a clinically suspected metal hypersensitivity reaction. Thus, neither necrobiosis nor infiltration of T-lymphocytes should be considered to be specific for failed metal-on-metal bearings or metal hypersensitivity reaction.

How much vitamin D do we need for skeletal health?

BACKGROUND: Vitamin D is critical for musculoskeletal health and has been implicated in the risk of extraskeletal diseases, including cancer, cardiovascular diseases, and autoimmune diseases, as well as overall mortality. Although numerous studies deal and have dealt with vitamin D deficiency and its consequences, experts cannot agree on the right 25-hydroxyvitamin D levels. This survey aims to shed light on the ongoing vitamin D controversy from different angles. QUESTIONS/PURPOSES: We discuss the minimum threshold for the 25-hydroxyvitamin D level to guarantee optimal health, why vitamin is D critical to musculoskeletal and extraskeletal functions, and new evidence for the success of prevention measures such as food fortification. METHODS: We searched PubMed, Google Scholar, and reference lists of articles using several keywords. The most recent search was in February 2011. RESULTS: While the use of parathyroid hormone as a surrogate measure did not lead to a consensus concerning the required 25-hydroxyvitamin D serum level, the combined analysis of bone mineralization and vitamin D status has established minimum levels of more than 75 nmol/L (30 ng/mL) to guarantee at least skeletal health. An effective measure to approach this status is food fortification, which has been demonstrated by countries such as Canada, the United States, and Finland. CONCLUSIONS: Given the health economic implications of failure to maintain a balanced vitamin D status, action is recommended to integrate current scientific knowledge on vitamin D into physicians' treatment of patients and governmental policies on food fortification.

Morphologic analysis of periprosthetic fractures after hip resurfacing arthroplasty.

BACKGROUND: Periprosthetic fractures have long been recognized as one of the major complications of hip resurfacing arthroplasty. The objective of this study was to develop a systematic and morphologic classification of the fracture mode based on pathogenesis. METHODS: One hundred and seven retrieved specimens consisting of the femoral remnant and the femoral component of a total hip resurfacing arthroplasty that had failed as a result of a periprosthetic fracture were analyzed with regard to the morphologic failure mode. The location of the fracture line was used to differentiate the fractures. The fractures were also classified histopathologically as acute biomechanical, acute postnecrotic, or chronic biomechanical. RESULTS: Fifty-nine percent (sixty-three) of the fractures occurred within the bone inside the femoral component. Fifty-one percent (fifty-five) of the fractures were classified morphologically as acute postnecrotic; 40% (forty-three), as chronic biomechanical; and 8% (nine), as acute biomechanical. Acute biomechanical fractures were found exclusively in the femoral neck and occurred earlier (mean time [and standard deviation] between implantation and revision, 41 +/- 57 days) than acute postnecrotic fractures (mean time between implantation and revision, 149 +/- 168 days; p = 0.002) or chronic biomechanical fractures (mean time between implantation and revision, 179 +/- 165 days; p = 0.001). The latter two fracture types both occurred predominantly in the bone inside the femoral component. CONCLUSIONS: Three distinct fracture modes were characterized morphologically. Osteonecrosis was the most frequent cause of fracture-related failures. We suggest that an intraoperative mechanical injury of the femoral neck such as notching and/or malpositioning of the femoral component might lead to changes in the loading pattern or in the resistance to fracture of the femoral neck and may result in both acute and chronic biomechanical femoral neck fractures. These findings may serve as feedback information for the surgeon and possibly influence future therapeutic strategies.

Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients.

Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency therefore would be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals, excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters, including osteoid indices, were quantified using the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels were measured for all patients. Statistical analysis was performed by Student's t test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15% of the analyzed patients presented with an osteoid surface per bone surface (OS/BS) of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in osteoid volume per bone volume (OV/BV) greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of bone volume per trabecular volume (BV/TV) throughout all ages and affected both sexes equally. While we could not establish a minimum 25(OH)D level that was inevitably associated with mineralization defects, we did not find pathologic accumulation of osteoid in any patient with circulating 25(OH)D above 75 nmol/L. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25(OH)D below 75 nmol/L and strongly argue that in conjunction with a sufficient calcium intake, the dose of vitamin D supplementation should ensure that circulating levels of 25(OH)D reach this minimum threshold (75 nmol/L or 30 ng/mL) to maintain skeletal health.

Pathophysiology and Pathomorphology of Osteoporosis.

Osteoporosis is a disease that leads to fragility fractures due to the loss of bone mass and bone microstructure. This review presents an update on the fundamental pathophysiological and pathomorphological mechanisms of bone loss. Pathomorphological characteristics such as perforations and microcallus formations are explained. The physiological relevance of the remodeling process and its control by local paracrine, systemic endocrine, and central neural signaling pathways are discussed. Hormones, such as estrogen, follicle stimulating hormone, and leptin, transcription factors, such as Runx2 and osterix, and the wnt signaling pathway are discussed in terms of their roles in bone cell differentiation and function. On the basis of current knowledge, osteoporosis can be diagnosed and treated and fractures can be prevented. However, it is likely that new and even more effective diagnostic and therapeutic strategies will emerge as our understanding of the remodeling process that controls osteoblast and osteoclast function increases.

Postoperative Protocol in the Prevention of Fragility Fractures in Patients with Osteoporosis-Related Fractures.

Osteoporosis is a multifactorial disorder that requires advanced diagnostic evaluation tools. It should not be considered to be an inevitable disease entity or as a logical consequence of the physiological ageing process. Osteoporosis can be diagnosed and - more importantly - properly treated. It is therefore incomprehensible that most of the patients with diagnosed osteoporosis do not receive a specific pharmacotherapeutic treatment. Since orthopedic trauma surgeons most often see a patient with an osteoporosis-associated fracture on a first-hand basis, they, after providing adequate treatment of the fracture, must play a key role in initiating the primary diagnostics and therapy according to national or international guidelines for patients with previous osteoporotic fractures. Treatment should be closely coordinated with general practitioners so that a continuation of the therapy initiated in the hospital can be guaranteed. Basic measures for fracture prevention, including dietary supplements of calcium and vitamin D, should be recommended and implemented for all patients, whereas only those patients with the diagnosis of a manifest osteoporosis should receive a specific pharmacotherapy. Antiresorptive and anabolic drugs that are licensed for the treatment of men or postmenopausal women with osteoporosis have been shown to effectively reduce the incidence of vertebral and non-vertebral fractures. An evaluation of the treatment efficiency should also be performed, such as routine clinical re-evaluation and the measuring of the bone mineral density by dual X-ray absortiometry, every 18-24 months after the initiation of the pharmacotherapy.

The Second Most Common Bone Disease: A Review on Paget's Disease of Bone.

Paget disease of bone (PDB) is the second most common metabolic bone disease. It is a chronic disease with a mono- or polyostotic appearance that is characterized by an increased bone turnover. The orthopedic surgeon is often confronted with such symptoms and complications as bone pain, skeletal deformities, and pathologic fractures caused by the "out-of-balance bone remodeling process". Careful evaluation of the clinical and radiographic findings is necessary to determine whether treatment of PDB is indicated. The mode of action of effective pharmacological treatments consists of reducing the increase in osteoclast-mediated bone resorption that characterizes the disease. Bisphosphonates are the compounds of choice for PDB therapy; these are readily available and have received approval. Patients with PDB are at increased risk for surgical complications, such as blood loss and heterotopic bone formation, if operative treatment is necessary. However, advances in surgical techniques and accompanying medical treatment could potentially improve the overall outcome of these patients. To achieve that goal, careful perioperative interdisciplinary management and monitoring are essential.