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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Individuals with incident accelerated knee osteoarthritis have greater pain than those with common knee osteoarthritis progression: data from the Osteoarthritis Initiative

Clinical Rheumatology - We evaluated whether accelerated knee osteoarthritis (AKOA) was associated with greater pain and other outcomes and if outcomes varied over time differently among those with...     

Knee laxity after staircase exercise predicts radiographic disease progression in medial compartment knee osteoarthritis

Objective

To evaluate whether increased laxity of the knee during daily physical activities such as stair climbing is associated with progression of knee joint osteoarthritis (OA).

Methods

During the years 2001–2003, 136 patients with bilateral primary medial compartment knee joint OA were enrolled in this prospective study. Baseline data collected were body mass index (BMI), muscle power, radiographic joint space width, mechanical axis on standing radiography, and anteroposterior (AP) knee laxity before and after physical exercise. After 8 years of followup, 84 patients were reexamined to assess radiographic changes. Radiographic disease progression was defined as progression of >1 grade on the Kellgren/Lawrence scale.

Results

AP knee laxity increased significantly after stair climbing. Patients with OA progression and those without progression did not differ significantly in age, sex, baseline quadriceps muscle strength, mechanical axis, joint space width, and AP knee laxity before exercise. The 2 groups of patients did, however, differ significantly in baseline BMI and change in AP knee laxity due to exercise. The risk of progression of knee OA increased 4.15‐fold with each millimeter of increase in the change in AP knee laxity due to exercise and 1.24‐fold with each point increase in the BMI.

Conclusion

Our results indicate that patients with OA progression have significantly greater changes in knee joint laxity during physical activities and a higher BMI than patients without OA progression. These findings suggest that larger changes in knee laxity during repetitive physical activities and a higher BMI play significant roles in the progression of knee OA.

     

Dynamic load at baseline can predict radiographic disease progression in medial compartment knee osteoarthritis

OBJECTIVE: To test the hypothesis that dynamic load at baseline can predict radiographic disease progression in patients with medial compartment knee osteoarthritis (OA). METHODS: During 1991-93 baseline data were collected by assessment of pain, radiography, and gait analysis in 106 patients referred to hospital with medial compartment knee OA. At the six year follow up, 74 patients were again examined to assess radiographic changes. Radiographic disease progression was defined as more than one grade narrowing of minimum joint space of the medial compartment. RESULTS: In the 32 patients showing disease progression, pain was more severe and adduction moment was higher at baseline than in those without disease progression (n=42). Joint space narrowing of the medial compartment during the six year period correlated significantly with the adduction moment at entry. Adduction moment correlated significantly with mechanical axis (varus alignment) and negatively with joint space width and pain score. Logistic regression analysis showed that the risk of progression of knee OA increased 6.46 times with a 1% increase in adduction moment. CONCLUSIONS: The results suggest that the baseline adduction moment of the knee, which reflects the dynamic load on the medial compartment, can predict radiographic OA progression at the six year follow up in patients with medial compartment knee OA.     

Risk factors for incident radiographic knee osteoarthritis in the elderly. The framingham study

Objective. Knee osteoarthritis (OA) is highly prevalent, especially in the elderly. Preventive strategies require a knowledge of risk factors that precede disease onset. The present study was conducted to determine the longitudinal risk factors for knee OA in an elderly population. Methods. A longitudinal study of knee OA involving members of the Framingham Study cohort was performed. Weight-bearing knee radiographs were obtained in 1983–1985 (baseline) and again in 1992–1993. Incident disease was defined as the occurrence of new radiographic OA (Kellgren and Lawrence grade ⩾2 on a 0–4 scale) in those without radiographic OA at baseline. Risk factors assessed at baseline and in the interim were tested in univariate and multivariate equations to evaluate their association with incident knee OA. Results. Of 598 patients without knee OA at baseline (mean age 70.5 years, 63.7% women), 93 (15.6%) developed OA. After adjustment for multiple risk factors, women had a higher risk of OA than did men (adjusted odds ratio [OR] = 1.8, 95% confidence interval [95% CI] 1.1–3.1). Higher baseline body mass index increased the risk of OA (OR = 1.6 per 5-unit increase, 95% CI 1.2–2.2), and weight change was directly correlated with the risk of OA (OR = 1.4 per 10-lb change in weight, 95% CI 1.1–1.8). Physical activity increased the risk of OA (for those in the highest quartile, OR = 3.3, 95% CI 1.4–7.5). Smokers had a lower risk than did nonsmokers (for those who smoked an average of ⩾10 cigarettes/day, OR = 0.4, 95% CI 0.2–0.8). Factors not associated with the risk of OA included chondrocalcinosis and a history of hand OA. Weight-related factors affected the risk of OA only in women. Conclusion. Elderly persons at high risk of developing radiographic knee OA included obese persons, nonsmokers, and those who were physically active. The direction of weight change correlated directly with the risk of developing OA.     

Tenascin-C concentration in synovial fluid correlates with radiographic progression of knee osteoarthritis

OBJECTIVE: Osteoarthritis (OA) is a major cause of disability and represents the most common disease in the aging population. Although the course of the disease is generally assessed using standard radiographic images, biochemical markers may be employed to detect the disease and determine the degree of severity. We developed an enzyme linked immunosorbent assay (ELISA) system using a monoclonal antibody specific for the large-splice variants of tenascin-C (TN-C) and examined whether TN-C in synovial fluid (SF) is an adequate biochemical marker of OA progression. METHODS: SF samples were obtained from knees of 74 patients with OA and 16 without OA. Based on the radiographic grading of the OA severity, the knees were divided into 3 groups: mild, moderate, and severe OA. Expression of TN-C splice variants was examined using immunoblotting. TN-C concentrations were determined by ELISA. RESULTS: Western blotting showed the presence of large TN-C variants in SF from severe OA. TN-C levels were 5-fold higher in OA samples compared to subjects without OA (p < 0.0001). TN-C levels were not different between control cases and mild OA, but increased significantly in moderate (p = 0.0244) and severe OA (p < 0.0001). After adjusting TN-C levels for age, body mass index, and sex, TN-C levels correlated with radiographic progression of knee OA (R2 = 0.404, p < 0.0001). CONCLUSION: TN-C, including the large-variant subunits, is a useful biochemical marker for OA progression in the later stages of disease.     

Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee

OBJECTIVE: To analyze cross sectional data from the National Health and Nutrition Examination Survey (NHANES I) concerning 3 indicators of osteoarthritis (OA) of the knee: radiographic evidence of structural damage, self-reported knee pain, and self-report of a diagnosis of arthritis at any joint by a physician. METHODS: Analysis of NHANES I data for 6880 persons ages 25-74 in the United States. RESULTS: Radiographic stage 2-4 knee OA was found in 319 subjects (3.7%); only 47% of these individuals reported knee pain, and only 61% reported that a physician had told them that they had arthritis. Knee pain was reported by 1004 subjects (14.6%), only 15% of whom had radiographic stage 2-4 changes of OA, and 59% of whom reported having a diagnosis of arthritis by a physician. A report of arthritis diagnosed by a physician was given by 1762 subjects (25.6%), of whom only 11% had stage 2-4 radiographic knee OA and 34% reported knee pain. CONCLUSION: Substantial discordance exists in this population based study between radiographic OA of the knee versus knee pain, versus a diagnosis of arthritis by a physician. These phenomena may be important in the design of clinical research studies, as well as in criteria for OA.     

Measurement of joint space width in hip osteoarthritis: influence of joint positioning and radiographic procedure

OBJECTIVES: We assessed the influence of patient positioning and radiographic procedure, and defined a smallest detectable difference (SDD) in hip osteoarthritis (OA). METHODS: OA hip patients each had a standardized pelvic radiograph and, 5 min later, a modified pelvic radiograph with the feet internally rotated 5 degrees (part 1 of the study), the X-ray beam centred on the umbilicus (part 2), or another standardized pelvic radiograph (part 3). RESULTS: Corresponding mean differences in joint space width (JSW) measurements (limits of agreement) between views were +0.03 (-0.53 to +0.59), -0.31 (-1.15 to +0.53) and -0.02 (-0.48 to +0.44) mm. The two views differed significantly in mean JSW in part 2 of the study (P=1.6x10(-4)), but not in part 1 (P=0.375) and part 3 (P=0.580). The SDD estimate was 0.46 mm. CONCLUSIONS: Modifying the X-ray beam and foot rotation increases variability in JSW measurements. Use of urograms to evaluate radiological progression should be avoided. A change greater than 0.46 mm could define radiological hip OA progression.     

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

Objective

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.

Methods

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.

Results

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/m² and 30.2 ± 5.5 kg/m², 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.

Conclusion

Thigh muscle strength does not appear to predict incident radiographic OA, but does seem to predict incident symptomatic knee OA.     

Men's shoes and knee joint torques relevant to the development and progression of knee osteoarthritis

OBJECTIVE: To determine if men's dress shoes and sneakers increase knee joint torques and play the same role in the development and/or progression of knee osteoarthritis (OA) as women's high-heeled dress shoes. METHODS: Three-dimensional data regarding lower extremity torques and motion were collected during walking in 22 healthy men while (1) wearing dress shoes, (2) wearing sneakers, and (3) barefoot. Data were plotted and qualitatively compared; major peak values were statistically compared between conditions. RESULTS: The external knee varus torque in early stance was slightly greater with the dress shoes and sneakers, but this slight increase can be explained by the faster walking speed with shoes. No significant increases were found in any other of the sagittal, coronal, or transverse knee torques when walking with dress shoes and sneakers compared to barefoot. CONCLUSION: Men's dress shoes and sneakers do not significantly affect knee joint torques that may have relevance to the development and/or progression of knee OA.     

Is tibiofemoral osteoarthritis in the knee joint a new disease?

OBJECTIVES--To compare the prevalence of osteoarthritis (OA) of the hip, tibiofemoral and patellofemoral joints in a skeletal population. METHODS--A total of 785 adult English skeletons (695 Saxon or Mediaeval origin) were examined for OA using established criteria. RESULTS--Twenty nine skeletons had hip OA, compared with 14 with patellofemoral joint OA, and only four tibiofemoral joint OA. CONCLUSION--Tibiofemoral OA was far less prevalent in ancient skeletons than hip or patellofemoral disease. Tibiofemoral OA may be a 'new' disease.     

Bone mineral density and risk of incident and progressive radiographic knee osteoarthritis in women: the Framingham Study

OBJECTIVE: To examine the relations of bone mineral density (BMD) and change in BMD to risk of incident and progressive radiographic knee osteoarthritis (OA) in a longitudinal cohort study. METHODS: Female participants aged 63 to 91 years (mean age 71) in the Framingham Study received anteroposterior weight bearing knee radiographs at biennial examinations 18 (1983-85) and 22 (1992-93). Knee radiographs were given scores for global severity of OA (Kellgren-Lawrence scale: range 0 to 4) and for the presence of osteophytes and joint space narrowing (range 0 to 3). Femoral neck BMD was assessed using dual photon absorptiometry at examination 20 and dual x-ray absorptiometry at examination 22. We examined the relations of BMD at examination 20 and its change between examination 20 and examination 22 to incident and progressive knee OA, as well as to worsening of individual radiographic features adjusting for age, body mass index, and other potential confounding factors. RESULTS: In total, 473 women (ages 63 to 91 yrs) had complete assessments. Over 8 years of followup, risk of incident radiographic knee OA increased from 5.6% among women in the lowest age-specific quartile of BMD to 14.2, 10.3, and 11.8% among women in the 2nd, 3rd, and highest quartiles, respectively. Multivariate adjusted OR of incident OA for each increase quartile of BMD were 1.0, 2.5, 2.0, and 2.3, respectively (p for trend = 0.222). This was mainly reflected in an increased risk of osteophyte development. However, risk of progressive OA decreased from 34.4 to 22.0, 20.3, and 18.9% as BMD increased. Compared to those in the lowest quartile of BMD, adjusted OR for progressive disease were 0.3, 0.2, and 0.1 among women in the 2nd, 3rd, and highest quartiles (p for trend <0.001), respectively, mainly due to its effect on lowering the risk of joint space loss. Compared to those who lost BMD >0.04 g/cm2 over the followup period, women who gained BMD were at increased risk of incident but at a significantly decreased risk of progressive knee OA. BMD change was not associated with osteophyte development, but gain in BMD lowered the risk of joint space loss. CONCLUSION: High BMD and BMD gain decreased the risk of progression of radiographic knee OA, but may be associated with an increased risk of incident knee OA. The protective effect was mainly through its influence on reducing the risk of joint space loss. Our results offer insights into how bone may affect the course of the most common joint disease, and thus may have potential therapeutic implications.     

Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee

OBJECTIVE: Raised serum C reactive protein (CRP) and hyaluronate (HA) concentrations predict the progression of knee osteoarthritis (OA) in the long term but the consistency of these relations with time is unknown. The purpose of this work was therefore to determine if raised CRP and HA at entry and three years before entry (-3 years) predict radiological progression of knee OA in a group of patients between entry and five years. METHODS: Knee radiographs from 90 patients with knee OA at entry and five years follow up were assessed for progression of disease over five years. The concentrations of serum CRP and HA were measured at entry (n=90) and also in 40 serum samples available from -3 years. Odds ratios (OR) for predicting progression were calculated by logistic regression. RESULTS: Serum CRP at entry was not predictive of progression between entry and five years (OR 1.12, 95% CI 0.81, 1.55) but serum CRP at -3 years was predictive of progression (OR 1.90, 95% CI 1.01, 3.28). Serum HA concentration at entry predicted progression between entry and five years (OR 2.32, 95% CI 1.16, 4.66). CONCLUSION: These results are consistent with previous reports relating to HA, and suggest that raised serum CRP reflects events that precede a period of later radiographic progression in knee OA. However, because of the large overlap between groups, the serum CRP or HA concentration are not good predictors of individual patient progression and have a poor sensitivity and specificity.