Hypermobility Assessment in 1,004 Adult Patients Presenting with Hip Pain: Correlation with Diagnoses and Demographics.

BACKGROUND: The strength of the association between hypermobility and developmental dysplasia of the hip (DDH) in adults is unknown. We sought to analyze this relationship in a prospective, blinded, institutional review board-approved, observational study. The hypothesis was that the prevalence of generalized joint hypermobility (GJH) would be significantly higher in patients with hip dysplasia than in those with other hip diagnoses on the basis of clinical observations of joint laxity. METHODS: One thousand and four consecutive new patients (390 males and 614 females) seen over a 4-year period were evaluated for hypermobility of the hip using 2 criteria: the Beighton 9-point physical examination criteria and the Hakim-Grahame 5-item history questionnaire. Diagnosis, age, sex, and race were tested as predictors of hypermobility. Patient-reported outcome scores from the International Hip Outcome Tool (iHOT-12) and the modified Harris hip score (mHHS) were also assessed. RESULTS: DDH was the primary diagnosis in 33.2% of the patient population. Patients who had dysplasia without osteoarthritis (OA) had a significantly elevated prevalence of GJH (77.9%) compared with those with nondysplastic hips (32.8%; p < 0.0001) or with patients who had dysplasia and OA (35.7%; p < 0.0001) according to either method. The odds ratio (OR) for patients with DDH versus those with other diagnoses was 7.1 (95% confidence interval [CI]: 5.1 to 10.0). The prevalence of hypermobility was significantly greater in females than in males (OR = 4.2 [95% CI: 3.2 to 5.5]; p < 0.0001). The prevalence of GJH was inversely proportional to age. There was a significantly reduced prevalence of GJH observed in Hispanic patients (p < 0.05) compared with other races. GJH was not a predictor of patient-reported outcome scores (p = 0.51 for iHOT-12 and p = 0.44 for mHHS). CONCLUSIONS: To our knowledge, this study is the first to establish a strong association between hypermobility and DDH in adults, confirming the hypothesis. We recommend utilizing both the Beighton and Hakim-Grahame scoring systems together as routine components of the history and physical examination for patients with hip dysplasia. Further research is warranted to explore the genetic basis and potential causal relationships between soft-tissue laxity and skeletal dysplasia, as well as improvements in assessment tools. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Calcification of human articular knee cartilage is primarily an effect of aging rather than osteoarthritis.

OBJECTIVE: Pathologic calcification of articular cartilage in human knees is often associated with advanced age and conditions of osteoarthritis (OA). Coincidently, most studies that have characterized calcification in joint cartilage have examined populations that are aged and presenting with clinical symptoms. Generally, these studies rely upon relatively insensitive plain radiographs or synovial fluid crystal analyses to quantify calcium levels. The purpose of this study was to examine the relationship between cartilage calcification and aging in an unselected donor population of diverse age using highly sensitive calcification imaging. METHODS: A group of 106 knee blocks were obtained from 56 individual donors (25 females and 31 males, aged 12-74, avg. 50.3 years). Condylar surfaces were graded on a 4-point OA grading scale for cartilage degeneration. The condyles were cut into approximately 7-10mm thick slabs. Using a Faxitron radiography system, high-resolution images were taken of the slabs to specifically image calcification in cartilage. The quantified calcification areas were then analyzed and correlations with both OA grade and age were assessed. RESULTS: Every knee presented some measurable calcification. The relative calcium deposition had a significant positive correlation with age. This same positive correlation was seen between condyles showing grade 1 and 2 changes. OA grades higher than 2 did not present any further significant increase in calcium levels. CONCLUSION: These observations indicate that age rather than OA is the predominant factor driving progressive pathologic calcification in articular cartilage.

Long-term effect of sodium hyaluronate (Hyalgan) on osteoarthritis progression in a rabbit model.

BACKGROUND: Intra-articular (IA) hyaluronan (HA) injections are approved for the treatment of knee osteoarthritis (OA) pain. One of the currently available products is approved for repeat treatment courses. While HA is classed as a symptom-modifying agent, there is substantial evidence that this therapeutic modality also possesses disease-modifying activity. OBJECTIVE: A rabbit model of OA, anterior cruciate ligament transection (ACLT), was used to investigate the long-term effects of single and sequential courses of HA therapy on OA progression. DESIGN: One or two courses of five weekly IA injections of sodium hyaluronate (Hyalgan) average molecular weight, MW, of 500-730 kDa, or vehicle were administered to rabbits (N=10 per group), initiated 4 and 13 weeks (for groups that received a second course) after ACLT. Gross morphological and histomorphometric evaluations were performed on harvested knee joints following sacrifice at 26 weeks after surgery. RESULTS: All the rabbits exhibited the characteristic pathologic changes of OA. Rabbits that received one or two courses of HA injections showed less disease progression than rabbits treated with ACLT alone or with 10 vehicle injections. However, rabbits that received five vehicle injections also showed improved morphology compared with those given no injections. Rabbits that received 10 HA injections showed significantly less surface roughness of the femoral cartilage compared with rabbits treated with ACLT, 5 HA injections, or 10 vehicle injections, and showed significantly less surface roughness of the tibial plateau compared with all other treatment groups (P<0.05). CONCLUSIONS: Repeat courses of HA injections reduced the degree of articular degeneration in a rabbit ACLT model of OA. Sequential courses of HA therapy may be advantageous in the long-term management of OA.

Matrices for cartilage repair.

Techniques for repairing focal articular cartilage defects are evolving from methods that induce a local stimulation of fibrocartilaginous repair to methods that will lead to a hyaline articular cartilage repair. Mosaicplasty and autologous chondrocyte implantation are examples of the latter. A tissue engineered hyaline cartilage implant that could be used off the self would minimize the morbidity of these techniques. However, there are significant questions that still need to be resolved before such tissue-engineered implants will be practical. Principally among these is the question of what is the ideal matrix for such an implant, particularly from the standpoint of the best material and architecture. Second, what is the ideal cell source to use with these implants. A third major unknown is what is the most ideal way to use growth factors to enhance the repair. As these issues are resolved, the prospects of a tissue engineered cartilage replacement will advance from theory to practice.

The long-term effects of hyaluronan during development of osteoarthritis following partial meniscectomy in a rabbit model.

OBJECTIVE: The long-term effect of hyaluronan (HA) on meniscus remodeling and articular cartilage preservation was assessed during the development of osteoarthritis following partial meniscectomy in a rabbit model. DESIGN: Approximately 60% of the region of each medial meniscus of 20 rabbit knees was excised bilaterally. The left knee joint was treated with five weekly intraarticular injections of 0.3 ml of HA, beginning 1 week after surgery. The right control knee was injected with PBS on the same schedule. Six months after surgery, animals were killed and the medial menisci and tibial articular cartilage were evaluated morphologically, histologically and biochemically. RESULTS: Meniscal regeneration was observed as newly synthesized translucent tissue, and image analysis revealed that the amount of this tissue was significantly greater in the HA-treated menisci than in the vehicle-treated menisci. Safranin-O staining and image analysis revealed the increased presence of glycosaminoglycans in the HA-treated menisci relative to vehicle-treated menisci while vascularity and biochemical parameters (hydration, total GAGs and reducible collagen crosslinks) were statistically similar in HA- and vehicle-treated menisci. Gross morphologic grading with India ink revealed a trend for less deterioration of tibial articular cartilage in the HA group (P=0.09) while Mankin's score of the HA-treated tibial articular cartilage was marginally lower than that of the vehicle group (P=0.06). Biochemical assessments showed a trend for higher total GAGs concentration in the HA-treated articular cartilage when compared to the vehicle treatment group (P=0.06). CONCLUSION: The present study has demonstrated that following partial meniscectomy, treatment with hyaluronan can enhance meniscal regeneration and may inhibit articular cartilage degeneration as long as six months post surgery.

Novel method for the quantitative assessment of cell migration: a study on the motility of rabbit anterior cruciate (ACL) and medial collateral ligament (MCL) cells.

A novel method of quantitating cell migration has been proposed for the potential utilization of tissue engineered scaffolds. Applying Alt's conservation law to describe the motion of first passage ACL and MCL cells, we have developed a quantitative method to assess innate differences in the motility of cells from these two ligamentous tissues. In this study, first passage ACL and MCL cells were cultured from four mature New Zealand white rabbits. One side of the cell monolayer was scraped completely away to create a wound model. The cell moved into the cell-free area, and cell density profiles were analyzed at 6 h and 12 h. Values of the random motility coefficient (mu) were then estimated by curve fitting the 6 h and 12 h data to a mathematical model, derived from the conservation law of cell flux. During 6 h of incubation in medium supplemented with 1% FBS, MCL cells (mu(MCL) = 4.63 +/- 0.65 X 10(-6) mm(2)/sec) were significantly (p < 0.05) more mobile than ACL cells (mu(ACL) = 2.51 +/- 0.31 X 10(-6) mm(2)/sec). At 12 h, the MCL cells also appeared to move faster (mu(ACL) = 4.39 +/- 0.63 X 10(-6) mm(2)/sec, mu(MCL) = 6.59 +/- 1.47 X 10(-6) mm(2)/sec), but the difference was not statistically significant (p = 0.18). Exposure of the cells to growth factors PDGF-BB or bFGF for 6 h had no significant effect on the migration of the ACL and MCL cells. However, exposure of the ACL cells (p < 0.05) and the MCL cells (p = 0.19) to 1 ng/mL of PDGFBB for 12 h enhanced their migration. Incubation with a high concentration (100 ng/mL) of PDGF-BB or bFGF at concentrations tested (1 or 100 ng/mL) for 12 h, produced little or no migratory stimulation on these ligament cells. Our findings support the previous qualitative observations made by numerous investigators. The novel methodology developed in this study may provide a basis for tissue engineering, and the results may be applied to tissue reconstruction techniques of the knee ligaments.

Method of histomorphometric assessment of glycosaminoglycans in articular cartilage.

A method of image analysis has been developed for use in the semiquantitative histomorphometric assessment of glycosaminoglycans in articular cartilage stained with safranin O. The reliability of the methodology is reported along with its application to the assessment of articular cartilage in a model of osteoarthritis, i.e., transection of the anterior cruciate ligament in rabbits. With this system, specimens of normal and osteoarthritic articular cartilage were assessed histomorphometrically for the following parameters: total cartilage area, percentage of safranin O stained area, mean gray scale (average stain intensity), and gray scale index (the relative total amount of glycosaminoglycans). Reproducibility was established for 12 specimens of normal cartilage and found to have a SD of less than 8% of the mean for each parameter that was measured. Image analysis of osteoarthritic cartilage revealed each of the parameters, except for average stain intensity, to be significantly lower than that in control cartilage.

A methodology for the quantitative assessment of articular cartilage histomorphometry.

OBJECTIVE: Traditionally, histological analysis of cartilage and cartilage repair has been performed qualitatively. While new techniques and grading systems have attempted to improve the quantitative nature of histological assessment, the advent of computer-based analysis systems have enabled development of more quantitative methodologies for cartilage repair. The objective of this study was to develop such a methodology for a more quantitative assessment of cartilage repair using a color-based image analysis system. DESIGN: Repair parameters were defined to describe the degree of cartilage restoration: repair dimensions, degree of attachment, surface roughness and repair location. This technique was experimentally applied to a cartilage repair study using cultured perichondrial cells implanted in a polylactic acid matrix in the rabbit femoral condyle. Specimens were examined and compared with the contralateral normal knee. RESULTS: Results showed increases in cartilage height, repair area, and surface roughness over controls for both 6 and 12 weeks. Surface elevation was significantly decreased at 6 weeks over 12 weeks. The percentage of repair improved between 6 and 12 weeks. Results were compared with a traditional grading system and demonstrated close correlation. Intraobserver and interobserver precision analysis were performed and demonstrated the reproducibility of the quantitative results by and between individuals. CONCLUSIONS: The methodology was deemed successful for a more objective analysis of cartilage with the added advantage of providing measured parameters that can assist in making comparisons between different studies using the same methodology.