Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis.

OBJECTIVE: Abnormal remodeling of subchondral bone (SB) induced by estrogen deficiency has been shown to be involved in osteoarthritis (OA). Raloxifene (RAL) is commonly used to treat postmenopausal osteoporosis (OP). However, little is known about its effects on OA combined with estrogen deficiency. This study was performed to evaluate the efficacy of RAL on patella baja-induced patellofemoral joint OA (PFJOA) in an ovariectomized rat model. DESIGN: Patellar ligament shortening (PLS) and ovariectomy (OVX) were performed simultaneously in 3-month-old female Sprague-Dawley rats, which were treated with RAL (10 mg/kg/day) or vehicle at 72 h postoperatively for 10 weeks. PFJOA was assessed by immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), micro-computed tomography (µCT), histomorphology and behavioral analyses. RESULTS: X-ray examinations showed that patella baja was successfully established by PLS. Histomorphological analysis revealed that PFJOA was significantly exacerbated by OVX and markedly alleviated by RAL. Moreover, RAL improved cartilage metabolism by decreasing MMP-13, ADAMTS-4, and caspase-3 and increasing Col-II and aggrecan at both the protein and mRNA levels. Furthermore, RAL markedly improved bone mass and SB microarchitecture and reduced osteoclast numbers and the serum osteocalcin and CTX-I levels. Although RAL showed a trend toward reducing pain sensitivity based on mechanical allodynia testing, this result was not statistically significant. CONCLUSION: These findings demonstrate that RAL treatment retards PFJOA progression in an ovariectomized rat model, suggesting that it may be a potential candidate for amelioration of the progression of PFJOA accompanied by postmenopausal OP.

In vitro effect of caveolin-1 as a slow-release material on bone-tendon junction healing: A comparative study.

Bone tendon junction injury is hard to cure because of its special anatomical structure, and the treatment applied for bone-tendon junction injury cannot result in the perfect vascular regeneration and restoration of the fibrocartilage zone. In this article, we aim to explore the effect of caveolin-1 as a slow-release material on bone-tendon junction healing. Seventy-two New Zealand rabbits were randomly selected and assigned into the experimental, sham-operated and control groups (n = 24). Caveolin-1 microspheres and microcapsule were developed as drug delivery system. At the 4th, 8th, and 12th weeks after surgery, quadriceps muscle patella-patellar tendon (QMPPT) was obtained from each rabbit to observe the tendon-to-bone tunnel healing, and X-ray examination, histological examination and biomechanical testing were applied for evaluating new bone formation. As the X-ray showed, caveolin-1 increased the new bone area at each time point. At the 4th and 8th weeks after surgery, the rabbit treated with caveolin-1 slow release material showed repair of fibrocartilage. According to the biomechanical results, the cross-sectional area, breaking load and ultimate tensile strength were increased along with time. At the same time point, caveolin-1 increased the ultimate tensile strength. Our study demonstrates that caveolin-1 as a slow-release material could accelerate bone-tendon junction healing by promoting the formation of the transition zone.

Limpet (Patella sp) as a biomonitor for organic pollutants. A proxy for mussel?

The scarcity of the most widely used species for assessing marine pollution (mussels) in some areas brings out the need to test the use of a different organism. In this study, 11 sampling sites along the Atlantic Spanish coast were selected and both mussels (Mytilus galloprovincialis) and limpets (Patella sp.) were analysed for PAHs, PBDEs and PCBs. The concentrations of the different pollutants in both species followed the same general distribution allowing us to differentiate polluted and unpolluted sites using any of them. Although the concentrations found in limpets were generally lower than those measured in mussels, a good correlation was observed for most of the groups of pollutants and also for every individual congener. A conversion factor was proposed for most of the individual PAH and PCB congeners, allowing the conversion of limpet concentration into mussel concentration that can be directly applied in assessments using environmental criteria derived for mussels.

Anti-arthritic properties of crude extract from Chenopodium ambrosioides L. leaves.

OBJECTIVES: To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. METHODS: Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. KEY FINDINGS: Treatment of CIA mice with HCE 5 mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. CONCLUSIONS: HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.

Study protocol: a double blind randomised control trial of high volume image guided injections in Achilles and patellar tendinopathy in a young active population.

BACKGROUND: Chronic tendinopathy is a significant problem particularly in active populations limiting sporting and occupational performance. The prevalence of patellar tendinopathy in some sports is near 50% and the incidence of lower limb tendinopathy is 1.4% p.a. in the UK Military. Management includes isometric, eccentric, heavy slow resistance exercises and extracorporeal shockwave therapy (ESWT). Often these treatments are inadequate yet there is no good evidence for injection therapies and success rates from surgery can be as low as 50%. High Volume Image Guided Injection (HVIGI) proposes to strip away the neovascularity and disrupt the nerve ingrowth seen in chronic cases and has shown promising results in case series. This study aims to investigate the efficacy of HVIGI in a randomised controlled trial (RCT). METHODS: RCT comparing 40ml HVIGI, with or without corticosteroid, with a 3ml local anaesthetic sham-control injection. Ninety-six participants will be recruited. INCLUSION CRITERIA: male, 18-55 years old, chronic Achilles or patellar tendinopathy of at least 6 months, failed conservative management including ESWT, and Ultrasound (US) evidence of neovascularisation, tendon thickening and echogenic changes. Outcome measures will be recorded at baseline, 6 weeks, 3, 6 and 12 months. Primary outcome measures include The Victoria Institute of Sport Assessments for Achilles and patellar tendinopathy (VISA-A and VISA-P) and VAS pain. Secondary outcome measures include Modified Ohberg score, maximum tendon diameter and assessment of hypoechoic appearance on US, and Functional Activity Assessment. DISCUSSION: Despite previous interventional trials and reviews there is still insufficient evidence to guide injectable therapy for chronic tendinopathy that has failed conservative treatment. The scant evidence available suggests HVIGI has the greatest potential however there is no level one RCT evidence to support this. Investigating the efficacy of HVIGI against control in a RCT and separating the effect of HVIGI and corticosteroid will add high level evidence to the management of chronic tendinopathy resistant to conservative treatment. TRIAL REGISTRATION: EudraCT: 2015-003587-36 3 Dec 2015.

Bone and bone marrow involvement in sarcoidosis.

Bone and bone marrow involvement in sarcoidosis have been infrequently reported. We aimed to describe the clinical features, radiological descriptions, pathological examinations, and outcomes of three patients with osseous sarcoidosis and one patient with bone marrow sarcoidosis seen at our institution. Our case series included fluorodeoxyglucose positron emission tomography descriptions in assessing the whole-body extent of sarcoidosis. In the era of advanced imaging, large bone and axial skeleton sarcoidosis lesions are more common than previously reported.

Metabolic and cytoprotective effects of in vivo peri-patellar hyaluronic acid injections in cultured tenocytes.

The purpose of this study was to investigate tenocyte mechanobiology after sudden-detraining and to examine the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained patellar tendon (PT) may reduce and limit detrained-associated damage in tenocytes. Twenty-four male Sprague-Dawley rats were divided into three groups: Untrained, Trained and Detrained. In the Detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Tenocyte morphology, metabolism and synthesis of C-terminal-propeptide of type I collagen, collagen-III, fibronectin, aggrecan, tenascin-c, interleukin-1ß, matrix-metalloproteinase-1 and-3 were evaluated after 1, 3, 7 and 10 days of culture. Transmission-electronic-microscopy showed a significant increase in mitochondria and rough endoplasmic reticulum in cultured tenocytes from Detrained-HA with respect to those from Detrained-NaCl. Additionally, Detrained-HA cultures showed a significantly higher proliferation rate and viability, and increased synthesis of C-terminal-Propeptide of type I collagen, fibronectin, aggrecan, tenascin-c and matrix-metalloproteinase-3 with respect to Detrained-NaCl ones, whereas synthesis of matrix-metalloproteinase-1 and interleukin-1ß was decreased. Our study demonstrates that discontinuing training activity in the short-term alters tenocyte synthetic and metabolic activity and that repeated peri-patellar infiltrations of HA during detraining allow the maintenance of tenocyte anabolic activity.

Repair of experimentally induced large osteochondral defects in rabbit knee with various concentrations of Escherichia coli-derived recombinant human bone morphogenetic protein-2.

Effective therapies for the regeneration of large osteochondral defects are still lacking; however, various approaches have been used. We evaluated the efficacy of Escherichia coli-derived dimeric recombinant human BMP-2 (E-rhBMP-2) for the repair of large osteochondral defects in a rabbit model. Osteochondral defects made in the femoral patellar groove of the knee were treated by transplanting gelatin sponges onto which no or various doses of E-rhBMP-2 were loaded. The outcomes were compared with those of an untreated control group four, 12 and 24 weeks after transplantation. At early time points, the cartilage tissue was repaired in a dose-dependent manner, and bone repair was accelerated in the defects treated with high doses of E-rhBMP-2. At 24 weeks, the repair of cartilage tissue was better with E-rhBMP-2 treatment, even at low doses, than without E-rhBMP-2 treatment. Our findings suggest that the use of E-rhBMP-2 improves and accelerates the repair of osteochondral defects in a rabbit model.

Dose-dependent osteoinductive effects of bFGF in rabbits.

Growth factors lead to the induction of tissue regeneration in bone healing when coated on biomaterials. Basic fibroblast growth factor (bFGF) combines osteoinduction and neoangiogenesis. This study evaluated bFGF-coated hydroxylapatite implants in two experimental groups with 10 or 100 microg (n = 5 per group) compared with uncoated control implants in the rabbit patellar groove model. We observed an unexpected ineffectiveness compared to the control groups with no significant difference of bone growth after 35 days. However, all samples from the 100 microg experiment (control and coated implant) showed significantly stronger 19-25 day label than both 10 microg groups (control and coated implant). Earlier bone labels are stronger in the 10 microg group with equal observation of similarity between experiment and control site and may indicate a possible inhibitory effect of the higher dosing or osteoclast induction. This result indicates a possible systemic effect of the transient growth factor coating.

Blocking of tumor necrosis factor activity promotes natural repair of osteochondral defects in rabbit knee.

BACKGROUND AND PURPOSE: Osteochondral defects have a limited capacity for repair. We therefore investigated the effects of tumor necrosis factor (TNF) signal blockade by etanercept (human recombinant soluble TNF receptor) on the repair of osteochondral defects in rabbit knees. MATERIAL AND METHODS: Osteochondral defects (5 mm in diameter) were created in the femoral patellar groove in rabbits. Soon after the procedure, a first subcutaneous injection of etanercept was performed. This single injection or, alternatively, 4 injections in total (twice a week for 2 weeks) were given. Each of these 2 groups was divided further into 3 subgroups: a low-dose group (0.05 microg/kg), an intermediate-dose group (0.4 microg/kg), and a high-dose group (1.6 microg /kg) with 19 rabbits in each. As a control, 19 rabbits were injected with water alone. The rabbits in each subgroup were killed 4 weeks (6 rabbits), 8 weeks (6 rabbits), or 24 weeks (7 rabbits) after surgery and repair was assessed histologically. RESULTS: Histological examination revealed that the natural process of repair of the osteochondral defects was promoted by 4 subcutaneous injections of intermediate-dose etanercept and by 1 or 4 injections of high-dose etanercept at the various time points examined postoperatively (4, 8, and 24 weeks). Western blot showed that rabbit TNFalpha had a high affinity for etanercept. INTERPRETATION: Blocking of TNF by etanercept enabled repair of osteochondral defects in rabbit knee. Anti-TNF therapy could be a strategy for the use of tissue engineering for bone and cartilage repair.

Ultrasound biomicroscopy imaging for monitoring progressive trypsin digestion and inhibition in articular cartilage.

This study reports an ultrasound biomicroscopy (UBM) imaging approach to monitor the progressive trypsin-induced depletion of proteoglycan (PG) and its inhibition in articular cartilage. Three fresh, normal bovine patellae were obtained and four full-thickness cartilage-bone specimens were prepared from the lower medial side of each patella. One sample was used as a control and the other three were divided into three groups: Groups A, B and C (n=3 for each group). After a 40min 0.25% trypsin digestion, samples from group A were continuously digested in trypsin solution, while those in groups B and C were immersed in physiologic saline and fetal bovine serum (FBS), respectively, for another 280min. The trypsin penetration front was observed by UBM and M-mode images were acquired using 50MHz focused ultrasound and custom-developed software. The results show that the 40min trypsin digestion degraded nearly the whole surface layer of the cartilage tissue. Further digestion in trypsin or residual digestion in saline for 280min depleted most of the PG content, as observed in groups A and B. The replacement of trypsin with a physiologic saline solution only slightly slowed the digestion process (group B), while trypsin inhibitors in FBS stopped the digestion in approximately 1.5h (group C). The normalized digestion fractions of the digested tissues were calculated from ultrasound data and histology sections, and then compared between the groups. Without the use of FBS, 80% to 100% of the full thickness was digested, while this number was only approximately 50% when using FBS. Our findings indicate that the UBM imaging system could provide two-dimensional (2-D) visual information for monitoring progressive trypsin-induced PG depletion in articular cartilage. The system also potentially offers a useful tool for preparing cartilage degeneration models with precisely controlled PG depletion.

Induction of chondrogenesis and expression of superficial zone protein (SZP)/lubricin by mesenchymal progenitors in the infrapatellar fat pad of the knee joint treated with TGF-beta1 and BMP-7.

Superficial zone protein (SZP) is a key mediator of boundary lubrication of articular cartilage in joints. In this investigation, we made the unexpected discovery that SZP was expressed in infrapatellar fat pad (IFP) from bovine knee. Quantitative analysis of secreted proteins in the medium of the IFP stromal cells demonstrated a significant stimulation by TGF-beta1 and BMP-7. Real-time PCR analysis revealed the SZP expression was up-regulated by TGF-beta1 and BMP-7. Chondrogenically differentiated IFP progenitor cells were stimulated by TGF-beta1 and BMP-7 to synthesize and secrete SZP. SZP mRNA was significantly up-regulated by chondrogenic induction for 21 days. These findings indicate that the stimulation of SZP expression by TGF-beta and BMP-7 may lead to functional improvement of damaged intraarticular tissues and that IFP progenitor cells may be a potential useful source for inducing superficial zone of articular cartilage by tissue engineering for regeneration of damaged articular cartilage due to osteoarthritis.

Human infrapatellar fat pad-derived stem cells express the pericyte marker 3G5 and show enhanced chondrogenesis after expansion in fibroblast growth factor-2.

INTRODUCTION: Infrapatellar fat pad (IPFP) is a possible source of stem cells for the repair of articular cartilage defects. In this study, adherent proliferative cells were isolated from digests of IPFP tissue. The effects of the expansion of these cells in fibroblast growth factor-2 (FGF-2) were tested on their proliferation, characterisation, and chondrogenic potential. METHODS: IPFP tissue was obtained from six patients undergoing total knee replacement, and sections were stained with 3G5, alpha smooth muscle actin, and von Willebrand factor to identify different cell types in the vasculature. Cells were isolated from IPFP, and both mixed populations and clonal lines derived from them were characterised for cell surface epitopes, including 3G5. Cells were expanded with and without FGF-2 and were tested for chondrogenic differentiation in cell aggregate cultures. RESULTS: 3G5-positive cells were present in perivascular regions in tissue sections of the IPFP, and proliferative adherent cells isolated from the IPFP were also 3G5-positive. However, 3G5 expression was on only a small proportion of cells in all populations and at all passages, including the clonally expanded cells. The cells showed cell surface epitope expression similar to adult stem cells. They stained strongly for CD13, CD29, CD44, CD90, and CD105 and were negative for CD34 and CD56 but were also negative for LNGFR (low-affinity nerve growth factor receptor) and STRO1. The IPFP-derived cells showed chondrogenic differentiation in cell aggregate cultures, and prior expansion with FGF-2 enhanced chondrogenesis. Expansion in FGF-2 resulted in greater downregulation of many cartilage-associated genes, but on subsequent chondrogenic differentiation, they showed stronger upregulation of these genes and this resulted in greater matrix production per cell. CONCLUSION: These results show that these cells express mesenchymal stem cell markers, but further work is needed to determine the true origin of these cells. These results suggest that the expansion of these cells with FGF-2 has important consequences for facilitating their chondrogenic differentiation.

The modulation of intra-articular inflammation, cartilage matrix and bone loss in mono-articular arthritis induced by heat-killed Mycobacterium tuberculosis.

Inflammation models for the assessment of anti-rheumatic drug activity utilize a variety of stimuli and sites. However, the determination of cartilage and bone degradation remains time consuming and problematic. A rapid rat model of Mycobacterium tuberculosis monoarticular arthritis with induces of inflammation, as well as patellar cartilage proteoglycan and bone degradation has been reported. This study characterizes this model with respect to the actions of anti-rheumatic drugs. Dexamethasone, cyclosporin and prednisolone inhibited all three parameters. Methotrexate inhibited joint inflammation alone, whilst azathioprine was without effect. Levamisole inhibited cartilage and bone degradation without affecting joint inflammation. NSAIDs were divided in their actions. Naproxen, piroxicam, diclofenac and tiaprofenic acid all inhibited joint inflammation and bone loss, but naproxen and piroxicam both significantly potentiated cartilage proteoglycan loss. This model appears to rely on cellular recruitment at this early stage, the anti-metabolites being ineffective. The modulation of inflammation can result in a protection against cartilage and bone damage in arthritis; however, certain NSAIDs are detrimental to cartilage integrity. The pharmacological manipulation of inflammatory arthritis can therefore dislocate inflammation from its effects on tissue destruction.

Repetitive mechanical stretching modulates IL-1beta induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts.

While mechanical loading is known to be essential in maintaining tendon homeostasis, repetitive mechanical loading has also been implicated in the etiology of tendon overuse injuries. The purpose of this study was to determine whether cyclic mechanical stretching regulates inflammatory responses induced by interleukin-1beta (IL-1beta) treatment in human patellar tendon fibroblasts (HPTFs). HPTFs were grown in microgrooved silicone dishes, where they became elongated in shape and aligned with the microgrooves, which is similar to the shape and organization of tendon fibroblasts in vivo. Cyclic uniaxial stretching was then applied to silicone culture dishes with a 4% or 8% stretch at a stretching frequency of 0.5 Hz for a duration of 4 h in the presence or absence of 10 pM IL-1beta treatment. Non-stretched cells in the presence or absence of IL-1beta were used for controls, respectively. The expression of cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), and the production of prostaglandin E2 (PGE2) were measured. In the absence of stretching, it was found that 10 pM of IL-1beta markedly induced higher levels of COX-2, MMP-1 gene expression, and PGE2 production than non-treated cells. Furthermore, cells with 4% stretching decreased the COX-2 and MMP-1 gene expression and PGE2 production that were stimulated by IL-1beta, whereas cells with 8% stretching further increased these gene products and/or expression levels in addition to the effects of IL-1beta stimulation. Thus, the results suggest that repetitive, small-magnitude stretching is anti-inflammatory, whereas large-magnitude stretching is pro-inflammatory. Therefore, moderate exercise may be beneficial to reducing tendon inflammation.

Repeated exposure of tendon to prostaglandin-E2 leads to localized tendon degeneration.

OBJECTIVE: To determine whether repeated exposure of rabbit patellar tendon to prostaglandin-E(2) leads to degenerative changes in the tendon. SETTING: Laboratory animal study. MAIN OUTCOME MEASURES: Intratendinous changes including cellularity, matrix organization, collagen fibril packing, and diameter. METHODS: Skeletally mature New Zealand White rabbits (n = 10) were transcutaneously injected in the midsubstance of the patellar tendon with prostaglandin-E(2) (PGE(2); 50 ng or 500 ng). The contralateral tendons were used as 3 different controls (no injection, saline injection, and needlestick only). The injection was repeated once a week for 4 weeks, and the rabbits were killed 1 week after the last injection. The patellar tendons were harvested and examined using hematoxylin and eosin staining and transmission electron microscopy. RESULTS: Compared with the control groups, tendons exposed to PGE(2) by injection showed focal areas of hypercellularity, loss of normal tissue architecture, and focal areas of tendon disorganization and degeneration. Tendons injected with PGE(2) exhibited loosely organized collagen fibrils and had thinner collagen fibril diameter compared with control tendons (P < 0.005). Tendons injected with 500 ng PGE(2) appeared to be more disorganized and degenerated than those injected with 50 ng PGE(2). CONCLUSIONS: Repeated exposure of the tendon to PGE(2) leads to degenerative changes within the tendon. CLINICAL RELEVANCE: It is known that human tendon fibroblasts produce PGE(2) in vitro and in vivo in response to repetitive mechanical loading. This study demonstrates that repetitive exposure of the tendon to PGE(2) can result in degenerative changes within the tendon. Therefore, PGE(2) produced by tendon fibroblasts in response to repetitive mechanical loading in vivo might contribute to the development of exercise-induced tendinopathy.

Ultrasonography as a tool for diagnosis, guidance of local steroid injection and, together with pressure algometry, monitoring of the treatment of athletes with chronic jumper's knee and Achilles tendinitis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: The diagnosis of Achilles and patella tendinitis has until recently been based on clinical examination, and treatment with local steroid injection has been given blindly. This is the first randomized, double blind, placebo-controlled study of local steroid injection in athletes with chronic tendinitis, which used ultrasonography to increase diagnostic accuracy, to guide the correct placement of local steroid and, conjunctively with pressure algometry, to objectify and monitor the results of treatment. METHOD: Forty-eight athletes each with severe symptomatic tendinitis of a patellar (24) or Achilles tendon (24) for more than 6 months, whose conditions were confirmed ultrasonographically, and who all failed conservative treatment (rehabilitation) were included in this double-blind, placebo-controlled study and treated with three ultrasonographically guided peritendinous injections of steroid or placebo. RESULTS: The conditions of only one-third of the referred athletes with clinically suspected tendinitis were confirmed by ultrasonographic examination. The ultrasonographically guided peritendinous injection of steroid had a significant effect in reducing pain and thickening of tendons. CONCLUSION: Ultrasonography should be used in the future to assure precise diagnosis and to guide the peritendinous injection of steroid in chronic Achilles and patella tendinitis. Ultrasonography and pressure algometry are recommended as objective methods for monitoring the effect of treatment. Ultrasonographically guided injection of long-acting steroid can normalize the ultrasonographic pathological lesions in the Achilles and patellar tendons, and has a dramatic clinical effect but when combined with aggressive rehabilitation with running after a few days, many will have relapse of symptoms within 6 months.

Effect of estrogen replacement therapy on patella cartilage in healthy women.

OBJECTIVES: Patellofemoral osteoarthritis (OA) is a significant cause of morbidity. Epidemiological data suggests that the use of oestrogen replacement therapy (ERT) may protect against tibiofemoral knee OA. However, the effect on patellofemoral OA is unknown. The aim of this study was to test the hypothesis that long term ERT (greater than 5 years) is associated with increased patella cartilage in post menopausal women. METHODS: We studied 81 women (42 current users (> 5 yrs) of oestrogen replacement therapy and 39 never users). Articular cartilage volumes were determined by post-processing images acquired in the sagittal plane using a T1-weighted fat suppressed magnetic resonance sequence on an independent workstation. RESULTS: There was no difference in the amount of patella cartilage in women on ERT compared to women on no ERT. After adjusting for patella bone size, years since menopause, body mass index, age of menopause and smoking, ERT users had 2.07 +/- 0.76 ml of patella cartilage compared to 1.93 +/- 0.89 ml in non-users (P = 0.24 for difference). CONCLUSIONS: This study suggests that use of ERT for more than 5 years does not have a significant effect on patella cartilage, in contrast to the previously described effect on tibial cartilage. The reasons for this are unknown, but may indicate that there are differences in the mechanisms for development of knee OA at these sites.