This study is based on a hypothesis that overexpression of an osteoclast enzyme, cathepsin K, causes an imbalance in bone remodeling toward bone loss. The hypothesis was tested in transgenic (TG) mice harboring additional copies of the murine cathepsin K gene (Ctsk) identifiable by a silent mutation engineered into the construct. For this study, three TG mouse lines harboring 3-25 copies of the transgene were selected. Tissue specificity of transgene expression was determined by Northern analysis, which revealed up to 6-fold increases in the levels of cathepsin K messenger RNA (

The functions of the intervertebral disc and of articular cartilage are intimately related to their aggrecan content. Aggrecan is a proteoglycan that interacts with hyaluronan to form large aggregates, which are responsible for the ability of the tissues to resist compressive loads. This function is related to the structure of aggrecan, and in particular to the large number of chondroitin sulphate chains present on its core protein. The chondroitin sulphate chains are present in two adjacent regions of the aggrecan core protein, termed the CS1 and CS2 domains. In the human, the region of the aggrecan gene encoding the CS1 domain exhibits size polymorphism, which can result in variation in the degree of chondroitin sulphate substitution of aggrecan in different individuals. This raises the possibility that the functional properties of aggrecan may vary between individuals, and that those individuals with an inferior aggrecan structure may be more susceptible to premature intervertebral disc or articular cartilage degeneration. Several studies have been performed to demonstrate such an association, but the results have been ambiguous. This review explains the relationship between aggrecan structure and function, describes the technique used to assess aggrecan polymorphism and the conclusions and limitations of the data obtained to date, and discusses the implications for tissue degeneration and clinical practice.

We have constructed cDNA clones covering the entire coding region of mouse, human and rabbit preprocathepsin K mRNA for studies on bone turnover. The clone pMCatK-1 for mouse cathepsin K shares 87% nucleotide homology with the corresponding human and rabbit sequences. Analysis of a panel of mouse tissues for tissue distribution of cathepsin K mRNA revealed the highest levels in musculoskeletal tissues: bone, cartilage and skeletal muscle. In situ hybridization of developing mouse embryos was performed to identify the cellular source of cathepsin K mRNA. The strongest mRNA signal was detected in osteoclasts of bone, identified in serial sections by positive TRAP staining. Cathepsin K mRNA was also observed in some hypertrophic chondrocytes of growth cartilages. Association of cathepsin K production with degradation of bone and cartilage matrix suggests that this enzyme and its mRNA levels could serve as markers for matrix degradation in diseases affecting these tissues.

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An experimental mouse model for disuse osteopenia was developed using unilateral cast immobilization. Analysis of the distal femurs and proximal tibias by quantitative histomorphometry revealed significant osteopenia within 10-21 days of immobilization. At 3 weeks, bone loss was also demonstrated with peripheral quantitative computed tomography as diminished bone mineral content and as concomitant reduction in the cross-sectional moment of inertia. These structural and geometrical alterations resulted in decreased strength of the distal femurs tested by cantilever bending. Analysis of the underlying cellular and molecular mechanisms of bone loss revealed a rapid increase in bone resorption within 3 days of immobilization. The mRNA levels for cathepsin K, matrix metalloproteinase-9, and tartrate resistant acid phosphatase were all significantly increased during the 21-day immobilization period, but with different expression profiles. These increases were paralleled by an increased number of osteoclasts as measured by histomorphometry. By day 6 of immobilization, the balance of bone turnover was further shifted toward net bone loss as the mRNA levels for major bone components (type I collagen and osteocalcin) were decreased. In histomorphometric analysis this was observed as reduced rates of mineral apposition and bone formation after 10 days of immobilization. The results of this study demonstrate that immobilization has a dual negative effect on bone turnover involving both depressed bone formation and enhanced bone resorption.

Background and purposeThe clinical findings of adverse reaction to metal debris (ARMD) following large-diameter-head metal-on-metal total hip arthroplasty (LDH MoM THA) may include periarticular fluid collections, soft tissue masses, and gluteal muscle necrosis. The ReCap-M2a-Magnum LDH MoM THA was the most commonly used hip device at our institution from 2005 to 2012. We assessed the prevalence of and risk factors for ARMD with this device.Methods74 patients (80 hips) had a ReCap-M2a-Magnum LDH MoM THA during the period August 2005 to December 2006. These patients were studied with hip MRI, serum chromium and cobalt ion measurements, the Oxford hip score questionnaire, and by clinical examination. The prevalence of ARMD was recorded and risk factors for ARMD were assessed using logistic regression models. The mean follow-up time was 6.0 (5.5–6.7) years.ResultsA revision operation due to ARMD was needed by 3 of 74 patients (3 of 80 hips). 8 additional patients (8 hips) had definite ARMD, but revision was not performed. 29 patients (32 hips) were considered to have a probable or possible ARMD. Altogether, 43 of 80 hips had a definite, probable, or possible ARMD and 34 patients (37 hips) were considered not to have ARMD. In 46 of 78 hips, MRI revealed a soft tissue mass or a collection of fluid (of any size). The symptoms clicking in the hip, local hip swelling, and a feeling of subluxation were associated with ARMD.InterpretationARMD is common after ReCap-M2a-Magnum total hip arthroplasty, and we discourage the use of this device. Asymptomatic patients with a small fluid collection on MRI may not need instant revision surgery but must be followed up closely.

Purpose. Biceps long head pathology is often associated with rotator cuff tears. The aim of this study was to determine the effect of possible associated biceps procedure on the treatment outcome in rotator cuff repair. Methods. 148 consecutive shoulders operated for isolated full-thickness supraspinatus tendon tear were included. A biceps tenotomy or tenodesis was performed in cases of irritated/frayed and/or unstable biceps tendon. The patients were grouped into three groups according to the biceps procedure (no procedure, tenotomy, and tenodesis). The age-adjusted Constant score was used as an outcome measure. Results. 145 shoulders (98%) were available for final followup. Preoperatively, there was no statistically significant difference in Constant scores. At three months, there was a statistically significant positive change in Constant scores compared with preoperative status in the tenotomy group in women. At one year there was a statistically significant positive change in Constant scores in all groups in both genders. However, there was no statistically significant difference between the groups at one year in either gender. Conclusion. Biceps procedure does not affect the final clinical treatment outcome after rotator cuff repair. Recovery from operative treatment may be faster in tenotomized female patients in cases of encountered biceps pathology.

A prospective long-term follow-up study of bioactive glass (BAG)-S53P4 and autogenous bone (AB) used as bone graft substitutes for posterolateral spondylodesis in treatment of degenerative spondylolisthesis during 1996 to 1998 was conducted. The surgical procedure was a standardized instrumented posterolateral fusion that used USS/VAS. BAG was implanted on the left side of the fusion bed and AB on the right side. The operative outcome was evaluated on x-rays and computed tomography scans, and a clinical examination was also performed. Seventeen patients (12 women, 5 men) participated in the 11-year follow-up. The mean Oswestry Disability Index score at the follow-up was 21 (range 0 to 52), compared with 49 (range 32 to 64) at the preoperative time. A solid bony fusion was seen on computed tomography scans on the AB side in all patients and on the BAG side in 12 patients. The fusion rate of all fusion sites (n=41) for BAG as a bone substitute was 88% at the L4/5 level and 88% at the L5/S1 level. The use of BAG as a bone graft extender can be considered as a good alternative in spinal surgery in the future.