Biomedical subjects

Changhai Ding

Publications and source records attributed to Changhai Ding.

At least 19 recordsLinked to original sources

PubMed2026

Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.

The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (p values ranged from 2.50 × 10-88 to 9.97 × 10-04). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (n = 362,286, all p < 0.05). Gene-drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (p = 7.08 × 10-08). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.

Humans↗

PubMed2025

Association Analysis of the Circulating Proteome With Sarcopenia-Related Traits Reveals Potential Drug Targets for Sarcopenia.

BACKGROUND: Sarcopenia severely affects the physical health of the elderly. Currently, there is no specific drug available for sarcopenia. This study aims to identify pathogenic proteins and druggable targets for sarcopenia through Mendelian randomization (MR)-based analytical framework. METHODS: A sequential stepwise screening method that includes two-sample MR, Steiger filtering test and colocalization (MRSC) was applied to identify causal proteins associated with sarcopenia-related traits. In the MR analyses, 4372 circulating proteins with valid instrumental variables (IVs) from eight proteomic genome-wide association studies were utilized as exposures, and nine sarcopenia-related traits were utilized as outcomes. IVs were classified into cis-protein quantitative trait loci (pQTLs) and trans-pQTLs based on their positions. We conducted cis-only MRSC analyses and cis + trans MRSC analyses using cis-pQTLs and cis + trans pQTLs as IVs, respectively. Post-MRSC analyses were conducted on the prioritized findings of MRSC, including annotation of protein-altering variants (PAVs), assessment of overlap between pQTLs and expression quantitative trait loci (eQTLs), protein-protein interaction (PPI) analysis, pathway enrichment analysis and annotation of drug targets. Utilizing data from the UK Biobank, we performed an observational study to explore the associations between baseline circulating protein levels and the longitudinal changes in nine sarcopenia-related traits. RESULTS: A total of 181 causal associations for 65 proteins were prioritized by the cis-only MRSC analyses and 227 associations for 91 proteins were prioritized by the cis + trans MRSC analyses. Among the prioritized proteins, the majority of them employed non-PAVs as IVs and most of their cis-pQTLs overlapped with corresponding eQTLs and exhibited consistent directionality, with only one trans-pQTL overlapping with an eQTL. The PPI network of cis-only MRSC-prioritized proteins (p = 4.04 × 10-4) and cis + trans MRSC-prioritized proteins (p = 8.76 × 10-5) showed significantly more interactions than expected. Reactome, KEGG and GO pathway enrichment analyses for cis-only MRSC-prioritized proteins identified 52, 12 and 79 enriched pathways, respectively (adjusted p < 0.05). For proteins identified by cis + trans MRSC analyses, only 15 pathways were enriched through the GO pathway enrichment analyses. In the observational study, 197 circulating proteins were identified to be associated with one or more sarcopenia-related traits (p < 0.05/2923). Among them, the significant associations of CTSB (negative association) and ASGR1 (positive association) with sarcopenia-related traits were observed to have consistent directional associations in both MR-based studies and observational studies. Drug target annotations suggested that 52 MRSC-prioritized proteins and 145 biomarkers are drug targets or druggable. CONCLUSIONS: This study identified 89 potential pathogenic proteins and 197 candidate biomarkers for sarcopenia, providing valuable clues for the development of therapeutic drugs for sarcopenia.

Humans↗

PubMed2007

A longitudinal study of the association between knee alignment and change in cartilage volume and chondral defects in a largely non-osteoarthritic population.

OBJECTIVE: It remains unclear whether malalignment of the knee is a cause of knee OA or a marker of disease progression. We investigated whether baseline malalignment of the knee predicts subsequent change in knee cartilage volume and chondral defects in subjects with and without radiographic knee osteoarthritis (OA). METHODS: A convenience sample of 315 male and female subjects (mean age 45 yrs, range 26-61) was followed up for a mean period of 2.4 years. Anatomic knee alignment was assessed on a standing anterior-posterior semiflexed view of the right knee and defined as the angle subtended by a line drawn through the midshaft of the femur with respect to one drawn through the midshaft of the tibia. T1-weighted fat saturation magnetic resonance imaging scans were performed on the same knee at baseline and followup for cartilage volume and chondral defects. RESULTS: Knee alignment was normally distributed in this sample with a mean of 178.2 degrees (SD 1.9 degrees). Fifty-five percent of subjects were < 178.5 degrees, while 14% were > 180 degrees. After adjustment for age, sex, body mass index, previous knee injury, and OA family history, neither category of alignment at baseline was associated with subsequent loss of lateral and medial tibial cartilage volume. Similarly, there was no association between malalignment and progression of chondral defects. The results remained the same when stratified by radiographic OA status. CONCLUSION: Our adequately powered study shows that baseline knee alignment is not associated with subsequent loss of cartilage volume or progression of chondral defects over 2 years. Further studies with a longterm followup are needed, but these results suggest malalignment is primarily a marker of disease progression.

Adult↗

PubMed2006

A longitudinal study of the effect of sex and age on rate of change in knee cartilage volume in adults.

OBJECTIVE: To describe the association between sex, age and rate of change in knee cartilage volume in adults. METHODS: A total of 325 subjects (mean age 45 yrs, range 26-61) was measured at baseline and approximately 2 yrs later. Knee cartilage volume and bone size were determined using T1-weighted fat saturation magnetic resonance imaging (MRI). Height, weight, body mass index and radiographic osteoarthritis (ROA) were measured by standard protocols. RESULTS: Knee cartilage volume decreased by 1.5-4.2% per annum. In multivariable analysis, females had higher rates of change per annum in knee cartilage volume than males (medial tibia: -3.5%, P < 0.001; lateral tibia: -2.6%, P < 0.001 and patella: -0.8%, P = 0.053). The sex difference first appeared at age 40 and became more marked with increasing age at the medial tibial site only (P = 0.039). Age was significantly associated with annual change in knee cartilage volume at all three sites (beta = -0.06 to -0.12%/yr, all P < 0.05), and these associations were stronger in females. With the exception of the medial site (beta = -0.05/yr, P = 0.117 for ROA exclusion, and beta = -0.06%/yr, P = 0.056 for ROA adjustment), the association with age did not change when subjects with ROA were excluded from analyses or after further adjustment for ROA. CONCLUSIONS: Within the age range we studied, knee cartilage volume declines at a faster rate with increasing age. This is partly mediated by ROA at the medial tibial site only. Furthermore, women have substantially higher knee cartilage loss than men, and these sex differences first appear at age 40 and become more marked with increasing age, which has implications for prevention of cartilage loss from middle age.

Adult↗

PubMed2006

Correlates of knee pain in older adults: Tasmanian Older Adult Cohort Study.

OBJECTIVE: To describe the association between chondral defects, bone marrow lesions, knee and hip radiographic osteoarthritis (OA), and knee pain. METHODS: Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index. T1- and T2-weighted fat saturation magnetic resonance imaging was performed on the right knee to assess chondral defects and subchondral bone marrow lesions. Radiography was performed on the right knee and hip and scored for radiographic OA. Body mass index (BMI) and knee extension strength were measured. RESULTS: A total of 500 randomly selected men and women participated. The prevalence of knee pain was 48%. In multivariable analysis, prevalent knee pain was significantly associated with medial tibial chondral defects (odds ratio [OR] 2.32, 95% confidence interval [95% CI] 1.02-5.28 for grade 3 versus grade 2 or less; OR 4.93, 95% CI 1.07-22.7 for grade 4 versus grade 2 or less), bone marrow lesions (OR 1.44, 95% CI 1.04-2.00 per compartment), and hip joint space narrowing (OR 1.36, 95% CI 1.07-1.73 per unit), as well as greater BMI and lower knee extension strength. It was not significantly associated with radiographic knee OA. These variables were also associated with more severe knee pain. In addition, there was a dose response association between knee pain and number of sites having grade 3 or 4 chondral defects (OR 1.39, 95% CI 1.12-1.73 per site), with all subjects having knee pain if all compartments of the knee had these defects. CONCLUSION: Knee pain in older adults is independently associated with both full and non-full-thickness medial tibial chondral defects, bone marrow lesions, greater BMI, and lower knee extension strength, but is not associated with radiographic knee OA. The association between radiographic hip OA and knee pain indicates that referred pain from the hip needs to be considered in unexplained knee pain.

Bone Marrow Diseases↗

PubMed2006

Correlates of knee pain in younger subjects.

The aim of this study was to describe clinical, structural and biochemical factors associated with knee pain in younger subjects. A cross-sectional convenience sample of 371 male and female subjects (mean age, 45 years, range 26-61) was studied. Knee pain was assessed by questionnaire. Chondral defects, cartilage volume, and bone area of the right knee were determined using T1-weighted fat saturation magnetic resonance imaging (MRI). X-ray was performed on the same knee for the assessment of radiographic features of osteoarthritis. The urinary C-terminal cross-linking telopeptide of type II collagen (CTX-II) was measured by enzyme-linked immunosorbent assay (ELISA). Height and weight were measured by standard protocols and body mass index (BMI) was calculated. The prevalence of knee pain was 35% in this sample. Chondral defect scores (particularly femoral and patellar but not tibial) were significantly associated with knee pain in a dose-response fashion (all p<0.01). Cartilage volume and bone area were not associated with knee pain in multivariate analysis in this sample. Urinary CTX-II was higher in subjects with knee pain (p=0.04), but this became nonsignificant after adjustment for BMI and osteophytes (both of which were significant) suggesting potential mechanisms of effect. In conclusion, knee pain is significantly associated with non-full thickness chondral defects (particularly femoral and patellar), osteophytes, CTX-II, and obesity but not other factors. MRI and biochemical measures can add to radiographs in defining unexplained knee pain in younger subjects.

Adult↗

PubMed2006

Natural history of knee cartilage defects and factors affecting change.

BACKGROUND: Knee cartilage defects may play an important role in early osteoarthritis, but little is known about their natural history. METHODS: Knee cartilage defect score (range, 0-4), cartilage volume, and bone surface area were determined using T1-weighted fat-saturated magnetic resonance imaging in 325 subjects (mean age, 45 years) at baseline and 2 years later. RESULTS: Thirty-three percent of the subjects had a worsening (>or=1-point increase) and 37% of the subjects had an improvement (>or=1-point decrease) in cartilage defect score in any knee compartment during 2.3 years. A worsening in cartilage defect score was significantly associated with female sex (odds ratio [OR], 3.09 and 3.64 in the medial and lateral tibiofemoral compartments) and baseline factors, including age (OR, 1.05 per year in the medial tibiofemoral compartment), body mass index (OR, 1.08 in the lateral tibiofemoral compartment), tibiofemoral osteophytes (OR, 6.22 and 6.04 per grade), tibial bone area (OR, 1.24 and 2.07 per square centimeter), and cartilage volume (OR, 2.91 and 1.71 per milliliter in the medial tibiofemoral and patellar compartments). An improvement in cartilage defect score had similar but reversed associations with these factors (except for sex), including a decrease in body mass index (OR, 1.23 in the medial tibiofemoral compartment). CONCLUSIONS: Knee cartilage defects are variable, and changes are associated with female sex, age, and body mass index. Increases are associated with baseline cartilage volume, bone size, and osteophytes, suggesting a role for these in the pathogenesis of cartilage defects. Interventions such as weight loss may improve knee cartilage defects.

Adult↗

PubMed2006

Does diclofenac induce accelerated progression of hip and knee radiographic osteoarthritis? Comment on the article by Reijman et al.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Genetic mechanisms of knee osteoarthritis: a population-based longitudinal study.

To describe the differences in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis and age- and sex-matched controls with no family history of knee osteoarthritis, a population-based longitudinal study of 163 matched pairs (mean age 45 years, range 26 to 61) was performed at baseline and about 2 years later. Knee cartilage defect score (0 to 4), cartilage volume and bone size were determined with T1-weighted fat saturation magnetic resonance imaging. Body mass index (BMI), lower-limb muscle strength, knee pain, physical work capacity at 170 beats/minute (PWC170) and radiographic osteoarthritis were measured by standard protocols. In comparison with controls, offspring had higher annual knee cartilage loss (-3.1% versus -2.0% at medial tibial site, -1.9% versus -1.1% at lateral tibial site and -4.7% versus -3.7% at patellar site, all P < 0.05), a greater increase in medial cartilage defect score (+0.15 versus -0.01, P < 0.05) and a greater decline in PWC170 (-0.7 watts/kg versus -0.4 watts/kg, P < 0.01). There were no significant differences in change in BMI, lower-limb muscle strength, knee pain or tibial bone area between these two groups; however, the differences in knee cartilage loss and cartilage defect change decreased in magnitude and became non-significant after adjustment for baseline cartilage volume, tibial bone area, BMI and knee pain. This longitudinal study suggests that knee cartilage loss, change in cartilage defects and decrease in physical fitness all have roles in the development of knee osteoarthritis, which is most probably polygenic but may reflect a shared environment. Importantly, the cartilage changes are largely dependent on baseline differences in cartilage volume, tibial bone area, BMI and knee pain, suggesting that these factors might have a role in their initiation.

Adult↗

PubMed2006

Familial, structural, and environmental correlates of MRI-defined bone marrow lesions: a sibpair study.

The aim of this study was to estimate the heritability and describe the correlates of bone marrow lesions in knee subchondral bone. A sibpair design was used. T2- and T1-weighted MRI scans were performed on the right knee to assess bone marrow lesions at lateral tibia and femora and medial tibia and femora, as well as chondral defects. A radiograph was taken on the same knee and scored for individual features of osteoarthritis (radiographic osteoarthritis; ROA) and alignment. Other variables measured included height, weight, knee pain, and lower-limb muscle strength. Heritability was estimated with the program SOLAR (Sequential Oligogenetic Linkage Analysis Routines). A total of 115 siblings (60 females and 55 males) from 48 families, representing 95 sib pairs, took part. The adjusted heritability estimates were 53 +/- 28% (mean +/- SEM; p = 0.03) and 65 +/- 32% (p = 0.03) for severity of bone marrow lesions at lateral and medial compartments, respectively. The estimates were reduced by 8 to 9% after adjustment for chondral defects and ROA (but not alignment). The adjusted heritability estimate was 99% for prevalent bone marrow lesions at both lateral and medial compartments. Both lateral and medial bone marrow lesions were significantly correlated with age, chondral defects, and ROA of the knee (all p < 0.05). Medial bone marrow lesions were also more common in males and were correlated with body mass index (BMI). Thus, bone marrow lesions have a significant genetic component. They commonly coexist with chondral defects and ROA but only share common genetic mechanisms to a limited degree. They are also more common with increasing age, male sex, and increasing BMI.

Adult↗

PubMed2006

Belimumab Human Genome Sciences/Cambridge Antibody Technology/GlaxoSmithKline.

Belimumab, the lead in a series of human monoclonal antibodies against the human protein B-lymphocyte stimulator (BLyS), is under development by Human Genome Sciences, Cambridge Antibody Technology and GlaxoSmithKline for the potential treatment of autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). By January 2006, belimumab had completed phase II clinical trials in SLE and RA; a phase III clinical SLE trial is scheduled to begin later this year.

Adult↗

PubMed2006

Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome.

Vertex Pharmaceuticals Inc, in collaboration with Kissei Pharmaceutical Co Ltd, is developing VX-702, one of a series of second-generation, orally active p38 MAP kinase inhibitors, for the potential treatment of inflammation, rheumatoid arthritis and cardiovascular diseases. In June 2005, a phase II clinical trial of VX-702 was initiated in rheumatoid arthritis. In July 2006, Vertex was planning to file an IND in the second half of 2006.

Acute Disease↗

PubMed2005

Optimal sampling of MRI slices for the assessment of knee cartilage volume for cross-sectional and longitudinal studies.

BACKGROUND: MRI slices of 1.5 mm thickness have been used in both cross sectional and longitudinal studies of osteoarthritis, but is difficult to apply to large studies as most techniques used in measuring knee cartilage volumes require substantial post-image processing. The aim of this study was to determine the optimal sampling of 1.5 mm thick slices of MRI scans to estimate knee cartilage volume in males and females for cross-sectional and longitudinal studies. METHODS: A total of 150 subjects had a sagittal T1-weighted fat-suppressed MRI scan of the right knee at a partition thickness of 1.5 mm to determine their cartilage volume. Fifty subjects had both baseline and 2-year follow up MRI scans. Lateral, medial tibial and patellar cartilage volumes were calculated with different samples from 1.5 mm thick slices by extracting one in two, one in three, and one in four to compare to cartilage volume and its rate of change. Agreement was assessed by means of intraclass correlation coefficient (ICC) and Bland & Altman plots. RESULTS: Compared to the whole sample of 1.5 mm thick slices, measuring every second to fourth slice led to very little under or over estimation in cartilage volume and its annual change. At all sites and subgroups, measuring every second slice had less than 1% mean difference in cartilage volume and its annual rate of change with all ICCs > or = 0.98. CONCLUSION: Sampling alternate 1.5 mm thick MRI slices is sufficient for knee cartilage volume measurement in cross-sectional and longitudinal epidemiological studies with little increase in measurement error. This approach will lead to a substantial decrease in post-scan processing time.

Aged↗

PubMed2005

Factors associated with hip cartilage volume measured by magnetic resonance imaging: the Tasmanian Older Adult Cohort Study.

OBJECTIVE: To compare associations between anthropometric and lifestyle factors and femoral head cartilage volume/thickness and radiographic features of osteoarthritis (OA) and to provide evidence of construct validity for magnetic resonance imaging (MRI) assessment of femoral cartilage volume and thickness. METHODS: We studied a cross-sectional sample of 151 randomly selected subjects (79 men, 72 women; mean age 63 years) from the Tasmanian Older Adult Cohort Study. A sagittal T1-weighted fat-suppression MRI scan of the right hip was performed to determine femoral head cartilage volume, cartilage thickness, and size. An anteroposterior radiograph of the pelvis with weight bearing was performed and scored for radiographic evidence of OA in the right hip. Other factors measured were height, weight, leg strength, serum vitamin D levels, and bone mineral density. RESULTS: Hip cartilage volume was significantly associated with female sex, body mass index, and femoral head size, whereas hip cartilage thickness was significantly associated only with the size of the femoral head. Only female sex was significantly associated with the total radiographic OA score and the joint space narrowing (JSN) score, but not the osteophyte score. Radiographic JSN of the hip, especially axial JSN (but not osteophytes), was significantly correlated with hip cartilage volume and thickness. CONCLUSION: Femoral head cartilage volume and thickness have modest but significant construct validity when correlated with radiographic findings. Furthermore, the generally stronger associations with volume compared with radiographic OA suggest that MRI may be superior at identifying risk factors for hip OA.

Aged↗

PubMed2005

Association of cartilage defects with loss of knee cartilage in healthy, middle-age adults: a prospective study.

OBJECTIVE: The significance of asymptomatic knee cartilage defects in healthy individuals is not known. The aim of this study was to examine the association between cartilage defects in the knee and cartilage volume both cross-sectionally and longitudinally in healthy, middle-age adults. METHODS: Eighty-six healthy men and women (mean +/- SD age 53.8 +/- 8.8 years) underwent T1-weighted fat-suppressed magnetic resonance imaging of their dominant knees at baseline and at the 2-year followup visit. Knee cartilage volume was measured. Cartilage defects were scored according to a grading system (0-4) and as present (a defect score of > or = 2) or absent in the medial and lateral tibiofemoral compartments. RESULTS: Cartilage defects in the medial and lateral tibiofemoral compartments were very common (in 61% and 43% of subjects, respectively). Those with cartilage defects had a 25% reduction in medial tibial cartilage volume, a 15% reduction in lateral tibial cartilage volume, and a 19% reduction in total femoral cartilage volume relative to those with no cartilage defects in cross-sectional analyses (all P < 0.05). In the medial tibiofemoral compartment, the annual loss of tibial cartilage in those with cartilage defects was 2.5% (95% confidence interval [95% CI] 2.2%, 3.1%) compared with an annual loss of tibial cartilage of 1.3% (95% CI 0.5%, 2.0%) in those with no defects (P = 0.028), independent of other known risk factors for osteoarthritis (OA). CONCLUSION: These data suggest that the presence of asymptomatic, non-full-thickness medial tibiofemoral cartilage defects identifies healthy individuals most likely to lose knee cartilage in the absence of radiographic knee OA. Thus, interventions aimed at reducing or reversing cartilage defects may reduce the risk of subsequent knee OA.

Australia↗

PubMed2005

The genetic contribution to longitudinal changes in knee structure and muscle strength: a sibpair study.

OBJECTIVE: To estimate the heritability of longitudinal changes in knee cartilage volume, chondral defects, subchondral bone size, and lower limb muscle strength. METHODS: A sibpair design was used. Longitudinal changes in lateral and medial tibial cartilage volume and bone size, as well as progression of chondral defects, were determined on serial magnetic resonance images. Radiographs were obtained and scored for individual features of radiographic osteoarthritis (OA) at baseline. Lower limb muscle strength was measured by dynamometry. Heritability was estimated using the SOLAR software package. RESULTS: A total of 115 subjects (55 men and 60 women, mean age 45 years) from 48 families representing 95 sibling pairs were successfully followed up for a mean of 2.4 years. The adjusted heritability estimates for changes in cartilage volume were 73% for the medial compartment (P < 0.01) and 40% for the lateral compartment (P = 0.10). The adjusted heritability estimates for changes in bone size were 62% for the lateral compartment (P = 0.03) and 20% for the medial compartment (P = 0.22). The adjusted heritability estimate for changes in muscle strength was 64% (P = 0.01). The adjusted heritability estimates for progression of chondral defects were 80% for the lateral compartment (P = 0.06) and 98% for the medial compartment (P = 0.03). These estimates changed little after adjusting for each other and for the predominantly mild radiographic OA, with the exception of progression of chondral defects in the lateral compartment. CONCLUSION: Early longitudinal changes in knee structures of relevance to later OA, such as changes in medial tibial cartilage volume, lateral tibial bone size, progression of chondral defects, and muscle strength, have high heritability, most likely reflecting a strong genetic component and suggesting their potential to be studied in quantitative trait linkage and association analysis.

Adult↗

PubMed2005

Association of prevalent and incident knee cartilage defects with loss of tibial and patellar cartilage: a longitudinal study.

OBJECTIVE: To describe the association between prevalent and incident knee cartilage defects and loss of knee cartilage in male and female adults. METHODS: A convenience sample of 325 subjects (mean age 45 years; age range 26-61 years) was evaluated at baseline and approximately 2 years later. Knee cartilage volume, cartilage defect scores (0-4 scale), and joint surface area were determined using T1-weighted fat-suppression magnetic resonance imaging techniques. Height, weight, and radiographic evidence of osteoarthritis were measured by standard protocols. RESULTS: Multivariable analysis revealed that baseline cartilage defect scores at the medial tibia, lateral tibia, and patella had a dose-response association with the annual rate of change in knee cartilage volume at the corresponding site (beta = -1.3% to -1.2% per grade; P < 0.05 for all comparisons). In addition, an increase in knee cartilage defect score (change of > or =1) was associated with higher rates of knee cartilage volume loss at all sites (beta = -1.9% to -1.7% per year; P < 0.01 for all comparisons). Furthermore, a decrease in the knee cartilage defect score (change of less than or equal to -1) was associated with an increase in knee cartilage volume at all sites (beta = 1.0% to 2.7% per year; P < 0.05 for all comparisons). CONCLUSION: Prevalent knee cartilage defects are predictive of compartment-specific cartilage loss over 2 years. Both increases and decreases in knee cartilage defects are associated with changes in knee cartilage volume, which implies a potential for reversal of knee cartilage loss.

Adult↗

PubMed2005

Knee cartilage defects: association with early radiographic osteoarthritis, decreased cartilage volume, increased joint surface area and type II collagen breakdown.

OBJECTIVE: To generate hypotheses regarding the associations between knee cartilage defects and knee radiographic osteoarthritis (ROA), cartilage volume, bone size and type II collagen breakdown in adults. METHODS: A cross-sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61) was studied. Knee cartilage defect score (0-4) and prevalence (a defect score of > or =2), cartilage volume, and bone surface area were determined using T1-weighted fat saturation MRI. Urinary levels of C-terminal crosslinking telopeptide of type II collagen (U-CTX-II) were measured by enzyme-linked immunosorbent assay. Height, weight and ROA were measured by standard protocols. RESULTS: In multivariate analysis, the severity and prevalence of knee cartilage defects were significantly and independently associated with tibiofemoral osteophytes (regression coefficient (beta): +0.86 to +1.31/unit, odds ratio (OR): 2.97-3.68/unit, all P<0.05 with the exception of OR in lateral tibiofemoral compartment) and tibial bone area (beta: +0.11 to +0.25/cm2; OR: 1.33-1.58/cm2, all P<0.01). Knee cartilage defects were inconsistently associated with joint space narrowing after adjustment for osteophytes but consistently with knee cartilage volume (beta: -0.27 to -0.70/ml; OR: 0.16-0.56/ml, all P<0.01 except for OR at lateral tibial cartilage site P=0.06). Lastly, knee cartilage defect severity was significantly associated with U-CTX-II (Partial r=+0.18, P<0.001 for total cartilage defect score). CONCLUSION: Osteophytes and increasing knee bone size may be causally related to knee cartilage defects. Furthermore, knee cartilage defects may result in increased cartilage breakdown leading to decreased cartilage volume and joint space narrowing suggesting an important role for knee cartilage defects in early knee OA.

Adult↗