Incident Radiographic Osteoarthritis Research Articles

Cyst-like lesions of the knee joint and their relation to incident knee pain and development of radiographic osteoarthritis: the MOST study

To determine whether intra- and periarticular cyst-like lesions of the knee are associated with incident knee pain and incident radiographic knee osteoarthritis (OA). The Multicenter Osteoarthritis (MOST) Study is a cohort of individuals who have or are at high risk for knee OA. Using a nested case-control study design, we investigated the associations of cyst-like lesions (Baker's, meniscal and proximal tibiofibular joint (PTFJ) cysts, and prepatellar and anserine bursitides) with (1) incident pain at 15- or 30-month follow-up and (2) incident radiographic OA at 30-month follow-up. Baseline cyst-like lesions were scored semiquantitatively using the Whole Organ Magnetic Resonance Imaging Score (WORMS). Conditional logistic regression models were used to assess the relation between these lesions and the outcomes, adjusting for potential confounding factors (i.e., cartilage loss, meniscal damage, bone marrow lesions, synovitis and joint effusion, which were also scored using WORMS). Incident knee pain study included 157 cases and 336 controls. Prevalence of meniscal and PTFJ cysts in the case group was twice that in the control group [9 (6%) vs 9 (3%) and 9 (6%) vs 10 (3%), respectively]. Incident radiographic OA study included 149 cases and 298 controls. Prevalence of grade 2 Baker's cysts and PTFJ cysts in the case group was approximately four times that in the control group [16(11%) vs 9 (3%) and 6 (4%) vs 3 (1%), respectively]. However, none of the cyst-like lesions was associated with incident pain or radiographic OA after fully adjusted logistic regression analyses and correction of P-values for multiple comparisons. None of the analyzed lesions was an independent predictor of incident knee pain or radiographic OA. Intra- and periarticular cyst-like lesions are likely to be a secondary phenomenon seen in painful or OA-affected knees, rather than a primary trigger for incident knee pain or radiographic OA.

Hazard of Incident and Progressive Knee and Hip Radiographic Osteoarthritis and Chronic Joint Symptoms in Individuals with and without Limb Length Inequality

To examine the hazard of incident and progressive radiographic osteoarthritis (rOA) and chronic joint symptoms at the hip and knee by limb length inequality (LLI) in a large, community-based sample. A longitudinal cohort completed baseline (1991-97) clinical evaluation and identical followup assessment (1999-2003) (median followup time 5.9 yrs, range 3.0-13.1 yrs). LLI was defined at baseline as a measured difference between limbs ≥ 2 cm. The study groups with LLI data comprised 1583 participants with paired (baseline and followup) knee radiographs and 1453 participants with paired hip radiographs. Multivariable Cox regression models were used to examine the hazard of incident and progressive knee and hip rOA and chronic joint symptoms, with adjustment for demographic and clinical factors. The hazard of developing incident knee or hip rOA was 20%-30% higher and of developing progressive knee or hip rOA was 35%-83% higher among participants with LLI, but results were only statistically significant for progressive knee rOA (adjusted hazard ratio = 1.83, 95% CI 1.10-3.05). The hazards of progressive chronic knee symptoms and incident and progressive chronic hip symptoms were 13%-59% higher among participants with LLI, but were not statistically significant. LLI was associated with progressive knee rOA and was nonsignificantly associated with incident knee or hip rOA and progressive hip rOA, progressive chronic knee symptoms, and incident and progressive chronic hip symptoms. Longer studies may strengthen these associations and help determine whether LLI is a risk factor or marker of these outcomes.

Do worsening knee radiographs mean greater chances of severe functional limitation?

Development of functional limitation is thought to be unrelated to changes in severity of radiographic osteoarthritis (OA) of the knee. We evaluated the relationship of change in radiographic OA to the incidence of severe functional limitation. Participants of the Multicenter Osteoarthritis Study, a cohort study of persons with or at high risk of knee OA, were evaluated at 0 and 30 months. Subjects were classified as having no, incident, stable, or worsening radiographic OA. Incidence of severe functional limitation was defined by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function scores (≥36.1/68) and walking speed (≤1.0 meter/second) at 30 months. The relationship of the change in radiographic OA to the incidence of severe functional limitation was evaluated by calculating risk ratios adjusted for potential confounders. Of the 2,210 subjects included (mean age 62 years, mean body mass index 30 kg/m², 60% women), 53% had no, 6% had incident, 14% had stable, and 27% had worsening radiographic OA. Persons with incident radiographic OA had 1.9 and 1.8 times the risk by WOMAC physical function score and walking speed, respectively, to have incident severe functional limitation compared with those with no radiographic OA over 30 months. Compared with those with stable radiographic OA, persons with worsening radiographic OA had 2.2 and 2.3 times the risk of incident severe functional limitation, respectively. Changes in structural disease are associated with the development of severe functional limitations in persons with or even at high risk of knee OA.

Is a “false‐positive” clinical diagnosis of knee osteoarthritis just the early diagnosis of pre–radiographic disease?

In routine practice, diagnosis of knee osteoarthritis (OA) currently relies on the combination of conventional risk factors and the presence of cardinal signs and symptoms. However, their role in early diagnosis has received little attention compared with biomarker research. Using data from 122 adults ages ≥50 years with knee pain but no definite radiographic OA, we tested whether the clinical diagnostic probability of OA, based on risk factors, signs, and symptoms, was associated with subsequent incidence of radiographic OA 3 years later. Clinical diagnostic probability performed only modestly in discriminating incident radiographic knee OA (area under the receiver operating characteristic curve = 0.59, 95% confidence interval 0.49-0.70). Improving the measurement of conventional markers and using study designs that test the ability of new biomarkers to add to or replace conventional markers are priorities for research in the early diagnosis of OA.

Serum transforming growth factor-beta 1 is not a robust biomarker of incident and progressive radiographic osteoarthritis at the hip and knee: the Johnston County Osteoarthritis Project

To test whether serum transforming growth factor-beta 1 (TGF-beta1) predicts incident and progressive hip or knee radiographic OA (rOA). Serum TGF-beta1 was measured for 330 participants aged 45 years and older in the Johnston County Osteoarthritis Project, with paired longitudinal films available for 618 hips and 658 knees. Incident and progressive rOA were defined using Kellgren-Lawrence (K-L) grade as well as osteophyte (OST) and joint space narrowing (JSN) scores. Natural logarithm transformation was used to produce near-normal distributions for continuous TGF-beta1 (lnTGF-beta1). Separate multivariable Weibull regression models were used to provide hazard ratios (HRs) for a 1-unit increase lnTGF-beta1 with each rOA outcome, accounting for variable follow-up times and clustering by individual, adjusted for age, race, gender, and body mass index (BMI). Interaction terms were considered statistically significant at P<0.10. The mean (+/-SD) age of the sample was 61.9+/-9.7 years, the mean BMI was 30.3+/-6.9 kg/m(2), with 60.6% women and 42.4% AA. The mean (+/-SD) TGF-beta1 was 17.8+/-6.1 ng/ml; follow-up time was 6.1+/-1.3 years. There were no significant interactions by race or gender. HRs showed no significant relationship between lnTGF-beta1 and incident or progressive rOA, OST, or JSN, at the knee or the hip. Levels of TGF-beta1 do not predict incident or progressive rOA, OST, or JSN at the hip or knee in this longitudinal, population-based study, making it unlikely that TGF-beta1 will be a robust biomarker for rOA in future studies.

Serum transforming growth factor-beta 1 is not a robust biomarker of incident and progressive radiographic osteoarthritis at the hip and knee: the Johnston County Osteoarthritis Project

Serum transforming growth factor-beta 1 is not a robust biomarker of incident and progressive radiographic osteoarthritis at the hip and knee: the Johnston County Osteoarthritis Project

Effect of thigh strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal cohort

To assess whether knee extensor strength or hamstring:quadriceps (H:Q) ratio predicts risk for incident radiographic tibiofemoral and incident symptomatic whole knee osteoarthritis (OA) in adults ages 50-79 years. We followed 1,617 participants (2,519 knees) who, at the baseline visit of the Multicenter Osteoarthritis (MOST) Study, did not have radiographic tibiofemoral OA and 2,078 participants (3,392 knees) who did not have symptomatic whole knee OA (i.e., did not have the combination of radiographic OA and frequent knee symptoms). Isokinetic strength was measured at baseline, and participants were followed for development of incident radiographic tibiofemoral OA, or incident symptomatic whole knee OA at 30 months. Generalized estimating equations accounted for 2 knees per subject, and multivariable models adjusted for age, body mass index (BMI), hip bone mineral density, knee surgery or pain, and physical activity score. In the studies of incident radiographic and incident symptomatic knee OA, mean +/- SD ages were 62.4 +/- 8.0 years and 62.3 +/- 8.0 years, respectively, and mean +/- SD BMI scores were 30.6 +/- 5.8 kg/m(2) and 30.2 +/- 5.5 kg/m(2), respectively. Knee extensor strength and H:Q ratio at baseline significantly differed between men and women. Neither knee extensor strength nor the H:Q ratio was predictive of incident radiographic tibiofemoral OA. Compared with the lowest tertile, the highest tertile of knee extensor strength protected against development of incident symptomatic whole knee OA in both sexes (adjusted odds ratio 0.5-0.6). H:Q ratio was not predictive of incident symptomatic whole knee OA in either sex. Thigh muscle strength does not appear to predict incident radiographic OA, but does seem to predict incident symptomatic knee OA.

Vitamin D Status, Bone Mineral Density, and the Development of Radiographic Osteoarthritis of the Knee

To study the association between baseline vitamin D status, bone mineral density (BMD), and the development of radiographic osteoarthritis (ROA) of the knee in a large population-based cohort of men and women. A sample of 1248 subjects (728 women and 520 men) was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. At baseline, vitamin D dietary intake was determined, and BMD and 25-hydroxy vitamin D (25(OH)D) serum levels were measured. After a mean follow-up time of 6.5 years incidence and progression of knee ROA of was assessed. The mean vitamin D intake in our study population was 64 IU/d and the mean 25(OH)D level 66 nmol/L. Vitamin D levels were associated with baseline BMD, particularly in subjects with baseline knee ROA. Progressive ROA occurred in 5.1% of the participants in the highest tertile of vitamin D intake against 12.6% in the lowest tertile, resulting in an adjusted odds ratio of 7.7 (95% CI: 1.3-43.5). Both intake and levels of 25(OH)D were not significantly related to incident ROA. However, we found a significant interaction between vitamin D intake and BMD in the association with incident knee ROA (P = 0.03): in subjects with low lumbar spine BMD at baseline we observe an increasing incidence of knee ROA with decreasing vitamin D intake and serum levels. Low dietary vitamin D intake increases the risk of progression of knee ROA. Particularly in subjects with low baseline BMD, vitamin D status seems to influence the incidence and progression of knee ROA. Thus, improving the vitamin D status in the elderly could protect against the development and worsening of knee OA, especially in those with low BMD.

Supination-External Rotation Ankle Fractures: Stability a Key Issue

Stability is a key issue in treating supination-external rotation ankle fractures, but we do not know how it affects functional outcome and subsequent development of radiographic osteoarthritis. With a systematic literature review, we identified 11 clinical studies (Level IV evidence) published in peer-reviewed journals reporting on at least 10 ankles. Followup was at least 1 year. Two authors independently scored the quality of the studies using the modified Coleman Methodology Score; the mean score was 58 of 100, with substantial agreement between the two examiners. Four studies used a general health assessment questionnaire. Several literature limitations (debatable fracture stability criteria, few cohort studies with heterogeneous methodology, small patient numbers and limited followup in some studies) do not allow definitive conclusions. Of 213 stable fractures treated nonoperatively, 2.8% of ankles had radiographic osteoarthritis develop (18 years' mean followup) and 84% were free of symptoms. The incidence of radiographic osteoarthritis in 420 unstable fractures treated operatively was 20.9% at 5.5 years versus 65.5% at 6.8 years in 137 ankles treated nonoperatively. The complication rate in 355 operatively treated fractures was 10.4%. A medial malleolus fracture, female gender, older age, higher American Society of Anesthesiologists grade, smoking, and lower educational level negatively influenced general health outcome, physical function, and pain. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The association of proximal femoral shape and incident radiographic hip OA in elderly women

Variations in femoral head shape are reported to predict incident hip osteoarthritis (OA). This study evaluated if proximal femur shape at baseline was a risk factor for incident radiographic hip OA (RHOA) after 8.3 years of follow-up in a cohort of elderly Caucasian women. Supine pelvic radiographs were obtained as part of the Study of Osteoporotic Fractures (SOF) at baseline and Visit 5 (8.3 years later), and were scored for RHOA. A nested case-control study was performed: hips were eligible for inclusion if they had no prevalent RHOA in either hip at baseline. Cases of incident RHOA were defined as no RHOA at baseline and RHOA in their right hip present at Visit 5 [or right total hip replacement (THR) for OA between baseline for follow-up] and a random selection of one half of all incident RHOA cases plus right THR cases (n=102) were chosen. A random selection (n=249) of control subjects who had no RHOA in their right hip at both baseline and follow-up visit were included for comparison. The shape of the right proximal femur was outlined on a digitized baseline radiograph and a statistical image analysis technique, Active Shape Modeling (ASM), was used to generate 10 unique and independent "modes" or variations in shape, which explained 95% of the variance in the shape of the proximal femurs studied. Any hip shape was therefore described as the average shape plus a linear combination of these 10 independent modes of variation. The values for each of these 10 modes for each hip analyzed were entered into a logistic regression model as independent predictors of incident RHOA adjusting for covariates. The incident RHOA cases were slightly taller, heavier and had higher total hip bone mineral density (BMD) than control subjects (P<0.05), but were otherwise similar demographically. Results of ASM showed that Modes 1, 2 and 3 together explained 81% of the variance in proximal femur shape among all subjects analyzed. Modes 3, 5, 9 which accounted for 8.9%, 3.3% and 0.8% of the variance respectively, were significant predictors of incident RHOA with adjusted odds-ratios ranging from 1.61 to 1.99 (P<0.001) for every 1 standard deviation (SD) increase in the mode score. These results suggest that variations in the relative sizes of the femoral head and neck at baseline are modest determinants of incident RHOA in elderly Caucasian women.

Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women

This study evaluated the association between polymorphisms in the estrogen receptor (ER) alpha gene (ESR1) and prevalent and incident radiographic hip osteoarthritis (RHOA) in a large, well-defined prospective cohort of elderly Caucasian women. Prevalent and incident RHOA was evaluated from all available pelvis X-rays obtained from the Study of Osteoporotic Fractures at baseline and after a mean of 8.3 years. Evaluable DNA samples were available from 4746 of these subjects. RHOA cases were defined by published methods. The ESR1 polymorphisms at intron I (Pvu II for a T/C substitution and Xba I for an A/G substitution) were genotyped in the context of a multiplex polymerase chain reaction (PCR) amplification followed by allele-specific single nucleotide polymorphism (SNP) detection with immobilized oligonucleotide probes in linear arrays. Multiple logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) associated with the T/C and A/G polymorphisms. RHOA was present in 12.1% of subjects, of whom 325 had joint space narrowing (JSN) score > or =3 and 130 had an osteophyte score > or =2 and JSN score > or =2. There was a significant reduction in the odds of prevalent RHOA for individuals with the C/C compared to T/T genotype at the Pvu II site with an OR of 0.71 (95% CI: 0.55-0.92) (P=0.01). Adjustments for age, weight, height, hip Bone mineral density (BMD) and estrogen use did not alter the relationship between the C/C genotype and reduced risk of RHOA, with an OR of 0.71 (95% CI: 0.54-0.94) (P=0.01). The risk of incident RHOA was reduced for the Pvu II C/C compared to the T/T genotype (P=0.11). Also, the reduced risk of incident RHOA in C/C subjects varied by estrogen use. There was no association between the Xba I G/G or G/A genotypes and RHOA with OR of 0.82 (95% CI: 0.61-1.10) (P=0.19) compared to women with A/A genotype. We conclude that the C/C genotype of the ER alpha Pvu II polymorphism was associated with a modestly reduced risk of prevalent and incident RHOA in elderly Caucasian women. Additional work is required to understand how the intron I ESR1 polymorphism may alter joint degeneration.

Knee alignment does not predict incident osteoarthritis: The Framingham osteoarthritis study

To examine the relationship of knee malalignment to the occurrence of knee osteoarthritis (OA) among subjects without radiographic OA at baseline to determine whether malalignment is a risk factor for incident disease or simply a marker of increasing disease severity. We selected 110 incident tibiofemoral (TF) OA case knees (76 subjects) and 356 random control knees (178 subjects) from among participants in the Framingham Osteoarthritis Study. Case knees did not have OA at baseline (1992-1994 examination) but had developed OA (Kellgren/Lawrence grade>or=2) at followup (2002-2005 examination) (mean of 8.75 years between examinations). Control knees did not have OA at baseline. Standardized digital radiographs of the fully extended knee with weight-bearing were read using a standard protocol and eFilm viewing software. We measured the anatomic axis, the condylar angle, the tibial plateau angle, and the condylar tibial plateau angle. The interobserver intraclass correlation coefficient (ICC) ranged from 0.93 to 0.96 and the intraobserver ICC from 0.94 to 0.97. In a knee-specific analysis, we examined the relationship of each alignment measurement to the risk of TF OA using generalized estimating equations, adjusting for age, sex, and body mass index (BMI). We used the same approach to assess the association between each alignment measurement and the risk of medial TF OA. Subjects in the case population were older and had a higher BMI than the controls. The alignment values were normally distributed and were not different between the cases and the controls. After adjustment for age, sex and BMI, there was no significant increase in incident OA in the highest quartile compared with the lowest quartile category for any of the alignment measures (P for trend for anatomic axis and condylar tibial plateau angle was 0.83 and 0.80, respectively). Similar results were also observed for medial compartment OA. We found that baseline knee alignment is not associated with either incident radiographic TF OA or medial TF OA. These results suggest that malalignment is not a risk factor for OA, but rather is a marker of disease severity and/or its progression.

Effect of recreational physical activities on the development of knee osteoarthritis in older adults of different weights: The Framingham Study

To evaluate the long-term effect of recreational exercise on the development of knee osteoarthritis (OA) in a community-based cohort of older adults, many of whom were overweight or obese. Subjects were asked about recreational activities including walking or jogging for exercise and working up a sweat, and were asked to compare their activity levels with others. Subjects were then asked about knee pain and weight-bearing anteroposterior and lateral knee radiographs were obtained. Approximately 9 years later, subjects were reexamined for OA. Radiographs were read for OA features in both tibiofemoral and patellofemoral compartments and were scored for tibiofemoral joint space narrowing. To evaluate incident OA, we excluded knees with OA at baseline for all analyses and focused on 3 knee-specific outcomes: incident radiographic OA, symptomatic OA, and tibiofemoral joint space loss. After adjusting for age, sex, body mass index (BMI), knee injury history, and correlation between knees, we evaluated the association of each recreational activity with OA development. A total of 1,279 subjects underwent both baseline and followup examinations (mean age at baseline 53.2 years). Neither recreational walking, jogging, frequent working up a sweat, nor high activity levels relative to peers were associated with a decrease or increase in risk of OA. Joint space loss was also unaffected by activity. Persons with BMI above the median (27.7 kg/m(2) for men and 25.7 kg/m(2) for women; mean BMI >30 kg/m(2) for both) had no increases in risk of OA by different type of activity. Among middle-aged and elderly persons without knee OA, many of whom were overweight, recreational exercise neither protects against nor increases risk of knee OA.

Age-related quadriceps-dominant muscle atrophy and incident radiographic knee osteoarthritis

Muscle atrophy is common in the elderly. However, the etiologic role of muscle atrophy associated with osteoarthritis of the knee has not been studied in detail. We assessed the association between age-related muscle atrophy around the knee joint and incident radiographic osteoarthritis of the knee. Twenty-one women in their thirties and 17 women in their sixties participated. They had no history, symptoms, or objective findings of any knee problems, and none of the participants was limited in performing daily activities. Radiographs of the knee joint were graded for the presence of osteoarthritis, and the cross-sectional imaging around the knee joint was carried out using computed tomography. Incident radiographic osteoarthritis was observed in 6 of the 17 women in their sixties. Quadriceps-dominant muscle atrophy was marked in the elderly women with radiographic osteoarthritis. In a multivariate analysis, the risk of incident radiographic osteoarthritis of the knee was significantly increased among women with a higher hamstrings/quadriceps cross-sectional area ratio. The results suggest the possibility that age-related quadriceps-dominant muscle atrophy may play a role in the pathogenesis of osteoarthritis of the knee.

Acetabular dysplasia predicts incident osteoarthritis of the hip: The Rotterdam study

To investigate the association between acetabular dysplasia and the incidence of radiographic osteoarthritis (OA) of the hip in a population-based sample of elderly subjects. Radiographs of the hip at baseline and at followup (mean followup time 6.6 years) were evaluated in 835 men and women (age >or=55 years) from the Rotterdam Study. Subjects with a baseline Kellgren/Lawrence grade of 0 or 1 in both hips were included in the study. Incident radiographic OA of the hip was defined as a decrease of joint space width of the hip (>or=1.0 mm) at followup. Acetabular dysplasia was assessed using the center-edge angle and the acetabular depth. The association between acetabular dysplasia and incident radiographic hip OA was assessed by calculating odds ratios using multivariate regression analysis. In this study population with a mean +/- SD age of 65.6 +/- 6.5 years, 9.3% developed incident radiographic hip OA. Subjects with acetabular dysplasia (center-edge angle <25 degrees ) had a 4.3-fold increased risk for incident radiographic OA of the hip (95% confidence interval 2.2-8.7) compared with subjects without acetabular dysplasia. These associations were independent of known determinants of hip OA such as age, sex, and body mass index (BMI), but tended to be enhanced by female sex, heavy mechanical load, and low BMI. In a study population age >or=55 years, acetabular dysplasia is still a strong independent determinant of incident radiographic hip OA.

The relationship of bone density and fracture to incident and progressive radiographic osteoarthritis of the knee: the Chingford Study.

Investigators performing cross-sectional studies have reported small increases in bone mineral density (BMD) in subjects with osteoarthritis (OA). This study was undertaken to examine the association of bone mass with incident and progressive disease and to determine whether prior fractures influence the development of OA. Eight hundred thirty women had repeat knee radiographs 48 months from baseline. All radiographs were graded on the presence or absence of osteophytes and joint space narrowing (JSN). Incident knee OA was defined as new disease in the 715 women without knee OA at baseline. Progression was a change of at least one grade in the 115 women with baseline knee OA. All women underwent bone densitometry of the lumbar spine and hip. Rates of subsequent incident OA were compared between fracture groups. The 95 women with incident knee osteophytes had significantly higher baseline spine BMD (1.01 gm/cm2 versus 0.95 gm/cm2, or 6.3%; P = 0.002) and significantly higher hip BMD (0.79 gm/cm2 versus 0.76 gm/cm2, or 3.9%; P = 0.02) than those without incident disease. For the 33 women whose osteophytes progressed, no difference was seen compared with nonprogressors in spine BMD, but hip BMD was modestly reduced (-2.5%). The 81 women who had incident JSN had nonsignificantly higher baseline spine BMD (3.0%), while no difference was seen for the 30 women whose JSN had progressed. For hip BMD, a nonsignificant increase was seen in those with incident JSN (1.3%), and a nonsignificant reduction was seen in those whose JSN progressed (-2.7%). One hundred forty-five women sustained peripheral fractures, mainly in the distal forearm (27.6%) and vertebrae (28.3%). Women with a peripheral fracture had a reduced risk of subsequently developing incident knee OA (odds ratio [OR] 0.30, 95% confidence interval [95% CI] 0.11-0.84). Although numbers were smaller, nonsignificant reductions in rates of incident OA were seen for those with distal forearm (OR 0.40, 95% CI 0.11-1.49) and vertebral (OR 0.20, 95% CI 0.07-1.61) fractures. These results confirm that for women who develop incident knee OA, defined by osteophytes, BMD is higher and of a magnitude similar to that shown in cross-sectional studies. Low BMD at the hip appears weakly related to progression. Women with previous fractures have less chance of developing OA, independent of BMD status. Although the mechanism for this action is unclear, these results suggest a possible common role of bone turnover and repair in the early manifestations of OA.

The relationship of bone density and fracture to incident and progressive radiographic osteoarthritis of the knee: The Chingford study

Investigators performing cross-sectional studies have reported small increases in bone mineral density (BMD) in subjects with osteoarthritis (OA). This study was undertaken to examine the association of bone mass with incident and progressive disease and to determine whether prior fractures influence the development of OA.Eight hundred thirty women had repeat knee radiographs 48 months from baseline. All radiographs were graded on the presence or absence of osteophytes and joint space narrowing (JSN). Incident knee OA was defined as new disease in the 715 women without knee OA at baseline. Progression was a change of at least one grade in the 115 women with baseline knee OA. All women underwent bone densitometry of the lumbar spine and hip. Rates of subsequent incident OA were compared between fracture groups.The 95 women with incident knee osteophytes had significantly higher baseline spine BMD (1.01 gm/cm2 versus 0.95 gm/cm2, or 6.3%; P = 0.002) and significantly higher hip BMD (0.79 gm/cm2 versus 0.76 gm/cm2, or 3.9%; P = 0.02) than those without incident disease. For the 33 women whose osteophytes progressed, no difference was seen compared with nonprogressors in spine BMD, but hip BMD was modestly reduced (-2.5%). The 81 women who had incident JSN had nonsignificantly higher baseline spine BMD (3.0%), while no difference was seen for the 30 women whose JSN had progressed. For hip BMD, a nonsignificant increase was seen in those with incident JSN (1.3%), and a nonsignificant reduction was seen in those whose JSN progressed (-2.7%). One hundred forty-five women sustained peripheral fractures, mainly in the distal forearm (27.6%) and vertebrae (28.3%). Women with a peripheral fracture had a reduced risk of subsequently developing incident knee OA (odds ratio [OR] 0.30, 95% confidence interval [95% CI] 0.11-0.84). Although numbers were smaller, nonsignificant reductions in rates of incident OA were seen for those with distal forearm (OR 0.40, 95% CI 0.11-1.49) and vertebral (OR 0.20, 95% CI 0.07-1.61) fractures.These results confirm that for women who develop incident knee OA, defined by osteophytes, BMD is higher and of a magnitude similar to that shown in cross-sectional studies. Low BMD at the hip appears weakly related to progression. Women with previous fractures have less chance of developing OA, independent of BMD status. Although the mechanism for this action is unclear, these results suggest a possible common role of bone turnover and repair in the early manifestations of OA.

Higher grip strength increases the risk of incident radiographic osteoarthritis in proximal hand joints

Quadriceps strength may protect against knee osteoarthritis (OA), but muscle activity is a major determinant of forces at the hand joints. Gripping objects is a common task during which high muscular forces are sustained, particularly at the proximal hand joints (metacarpophalangeal (MCP) joints and thumb base). The association between maximal grip strength and incident OA at different hand joints was examined in a longitudinal study of radiographic hand OA. Subjects with higher maximal grip strength were at increased risk for development of OA in the proximal interphalangeal (PIP) joints, MCP and thumb base joints in men; and in the MCP in women. No association was found between maximal grip strength and incident distal interphalangeal (DIP) joints OA in men or women. The conclusion is that increased grip strength, which is the major force of loading across proximal hand joints, increases the risk of OA in those joints.

Reduced quadriceps strength relative to body weight: a risk factor for knee osteoarthritis in women?

To determine whether baseline lower extremity muscle weakness is a risk factor for incident radiographic osteoarthritis (OA) of the knee. This prospective study involved 342 elderly community-dwelling subjects (178 women, 164 men) from central Indiana, for whom baseline and followup (mean interval 31.3 months) knee radiographs were available. Lower extremity muscle strength was measured by isokinetic dynamometry and lean tissue (i.e., muscle) mass in the lower extremities by dual x-ray absorptiometry. Knee OA was associated with an increase in body weight in women (P = 0.0014), but not in men. In both sexes, lower extremity muscle mass exhibited a strong positive correlation with body weight. In women, after adjustment for body weight, knee extensor strength was 18% lower at baseline among subjects who developed incident knee OA than among the controls (P = 0.053), whereas after adjustment for lower extremity muscle mass, knee extensor strength was 15% lower than in the controls (P not significant). In men, in contrast, adjusted knee extensor strength at baseline was comparable to that in the controls. Among the 13 women who developed incident OA, there was a strong, highly significant negative correlation between body weight and extensor strength (r = -0.740, P = 0.003), that is, the more obese the subject, the greater the reduction of quadriceps strength. In contrast, among the 14 men who developed incident OA, a modest positive correlation existed between weight and quadriceps strength (r = 0.455, P = 0.058). No correlation between knee flexor (hamstring) strength and knee OA was seen in either sex. Reduced quadriceps strength relative to body weight may be a risk factor for knee OA in women.

Longitudinal analysis of the relationship between serum insulin-like growth factor-I and radiographic knee osteoarthritis

Objective: To examine the relation between serum insulin-like growth factor I (IGF-I) levels and both incident and progressive radiographic knee osteoarthritis (OA) in the Framingham Osteoarthritis Study.Design: Subjects had bilateral weight-bearing, anterior–posterior knee radiographs performed in 1983–1985 and again in 1992–1993. IGF-I levels were measured from blood specimens obtained in 1988–1989 by a competitive binding radio-immunoassay (RIA) after separation with octadecasilyl-silica cartridges of serum IGF-I from binding proteins. Participants without baseline radiographic OA [Kellgren and Lawrence grades (K&L)=0–1] were classified as having incident disease if they had K&L[mog3]2 grades at follow-up. Progressive OA was defined as an increase in K&L score of [mog3]1 in knees with baseline OA (K&L[mog3]2). All analyses were knee-based and sex-specific. We examined IGF-I tertiles in relation to the risk of incident and progressive radiographic OA separately, adjusting for age, body mass index (BMI), and baseline K&L score, and used generalized estimating equations to adjust for the correlation between fellow knees.Results: Four hundred and forty-one participants had knee radiographs and serum IGF-I levels measured. No associations were found for serum IGF-I levels and incident [women: OR=0.9 (0.6–1.7), men OR=1.2 (0.6–2.6)] or progressive [women OR=0.9 (0.6–1.6), men OR{moe0}0.9 (0.3–3.0)] radiographic knee OA in either sex. Neither did we observe any association between IGF-I and worsening of individual radiographic features of OA (i.e., osteophyte growth and joint space loss).Conclusion: In summary, this longitudinal study did not demonstrate any association of serum IGF-I and incident or progressive radiographic knee OA. Further studies are needed to clarify the role of IGF-I in OA.