D. Dore

Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial

Objectives To compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs). Methods Adults aged 50–80 years (n=59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton density-weighted fat saturation MR images at baseline, 6 and 12 months. Pain and function were measured using a visual analogue scale (VAS) and the knee injury and osteoarthritis outcome score (KOOS) scale. Results At baseline, mean VAS score was 54 mm and mean total BML area was 468 mm2. VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months (−14.5 mm, 95% CI −28.1 to −0.9) but not after 3 or 12 months. Changes on the KOOS scales were not significant at any time point. Reduction in total BML area was greater in the ZA group compared with placebo after 6 months (−175.7 mm2, 95% CI −327.2 to −24.3) with a trend after 12 months (−146.5 mm2, 95% CI −307.5 to +14.5). A greater proportion of those in the ZA group achieved a clinically significant reduction in BML size at 6 months (39% vs 18%, p=0.044). Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms. Conclusions ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months. Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach. Clinical trial registration number ACTRN 12609000399291.

Natural history and clinical significance of MRI-detected bone marrow lesions at the knee: a prospective study in community dwelling older adults

IntroductionThere are conflicting data on the natural history and clinical significance of bone marrow lesions (BMLs). The aims of this study were to describe the natural history of MRI-detected BMLs at the knee using a quantitative measure and examine the association of BMLs with pain, function and stiffness scores, and total knee replacement (TKR) surgery.MethodsA total of 395 older males and females were randomly selected from the general population (mean age 63 years, range 52 to 79) and measured at baseline and approximately 2.7 years later. BMLs were determined using T2-weighted fat saturation MRI by measuring the maximum area of the lesion. Reproducibility was excellent (intraclass correlation coefficient (ICC): 0.97). Pain, function, and stiffness were assessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores. X-ray was used to assess radiographic osteoarthritis (ROA) at baseline.ResultsAt baseline, 43% (n = 168/395) had a BML. Of these 25% decreased in size and 24% increased. Of the remaining sample (n = 227), 7% developed a new BML. In a multivariable model, a change in BML size was associated with a change in pain and function scores (β = 1.13 to 2.55 per 1 SD increase, all P < 0.05), only in those participants without ROA. Lastly, baseline BML severity predicted TKR surgery (odds ratio (OR) 2.10/unit, P = 0.019).ConclusionsIn a population based sample, BMLs (assessed by measuring maximal area) were not static, with similar proportions both worsening and improving. A change in BML size was associated with changes in pain in those without established ROA. This finding suggests that fluctuating knee pain may be attributable to BMLs in those participants with early stage disease. Baseline BMLs also predicted TKR surgery. These findings suggest therapeutic interventions aimed at altering the natural history of BMLs should be considered.

Bone marrow lesions predict site-specific cartilage defect development and volume loss: a prospective study in older adults

IntroductionRecent evidence suggests that bone marrow lesions (BMLs) play a pivotal role in knee osteoarthritis (OA). The aims of this study were to determine: 1) whether baseline BML presence and/or severity predict site-specific cartilage defect progression and cartilage volume loss; and 2) whether baseline cartilage defects predict site-specific BML progression.MethodsA total of 405 subjects (mean age 63 years, range 52 to 79) were measured at baseline and approximately 2.7 years later. Magnetic resonance imaging (MRI) of the right knee was performed to measure knee cartilage volume, cartilage defects (0 to 4), and BMLs (0 to 3) at the medial tibial (MT), medial femoral (MF), lateral tibial (LT), and lateral femoral (LF) sites. Logistic regression and generalized estimating equations were used to examine the relationship between BMLs and cartilage defects and cartilage volume loss.ResultsAt all four sites, baseline BML presence predicted defect progression (odds ratio (OR) 2.4 to 6.4, all P < 0.05), and cartilage volume loss (-0.9 to -2.9% difference per annum, all P < 0.05) at the same site. In multivariable analysis, there was a significant relationship between BML severity and defect progression at all four sites (OR 1.8 to 3.2, all P < 0.05) and BML severity and cartilage volume loss at the MF, LT, and LF sites (β -22.1 to -42.0, all P < 0.05). Additionally, baseline defect severity predicted BML progression at the MT and LF sites (OR 3.3 to 3.7, all P < 0.01). Lastly, there was a greater increase in cartilage volume loss at the MT and LT sites when both larger defects and BMLs were present at baseline (all P < 0.05).ConclusionsBaseline BMLs predicted site-specific defect progression and cartilage volume loss in a dose-response manner suggesting BMLs may have a local effect on cartilage homeostasis. Baseline defects predicted site-specific BML progression, which may represent increased bone loading adjacent to defects. These results suggest BMLs and defects are interconnected and play key roles in knee cartilage volume loss; thus, both should be considered targets for intervention.

The association between objectively measured physical activity and knee structural change using MRI

Objectives This study describes the longitudinal association between objectively assessed physical activity (PA) and knee structural change measured using MRI. Methods 405 community-dwelling adults aged 51–81 years were measured at baseline and approximately 2.7 years later. MRI of the right knee at baseline and follow-up was performed to evaluate bone marrow lesions (BMLs), meniscal pathology, cartilage defects, and cartilage volume. PA was assessed at baseline by pedometer (steps/day). Results Doing ≥10 000 steps/day was associated with BML increases (RR 1.97, 95% CI 1.19 to 3.27, p=0.009). Participants doing ≥10 000 steps/day had a 1.52 times (95% CI 1.05 to 2.20, p=0.027) greater risk of increasing meniscal pathology score, which increased to 2.49 (95% CI 1.05 to 3.93, p=0.002) in those with adverse meniscal pathology at baseline. Doing ≥10 000 steps/day was associated with a greater risk of increasing cartilage defect score in those with prevalent BMLs at baseline (RR 1.36, 95% CI 1.03 to 1.69, p=0.013). Steps/day was protective against volume loss in those with more baseline cartilage volume but led to increased cartilage loss in those with less baseline cartilage volume. (p=0.046 for interaction). Conclusions PA was deleteriously associated with knee structural change, especially in those with pre-existing knee structural abnormalities. This suggests individuals with knee abnormalities should avoid doing ≥10 000 steps/day. Alternatives to weight-bearing activity may be needed in order to maintain PA levels required for other aspects of health.

Subchondral Bone and Cartilage Damage - A Prospective Study in Older Adults

OBJECTIVE There is limited longitudinal evidence relating subchondral bone changes to cartilage damage and loss. The aim of this study was to describe the association between baseline tibial bone area and tibial subchondral bone mineral density (BMD) with tibial cartilage defect development and cartilage volume loss. METHODS A total of 341 subjects (mean age 63 years, range 52-79 years) underwent measurement at baseline and approximately 2.7 years later. Tibial knee cartilage volume, cartilage defects (graded on a scale of 0-4), and bone area were determined using T1-weighted fat suppression magnetic resonance imaging. Tibial subchondral BMD was determined using dual x-ray absorptiometry. RESULTS In multivariable analysis, baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 per 1 SD increase, 95% confidence interval [95% CI] 1.0, 2.6, and OR 2.4 per 1 SD increase, 95% CI 1.4, 4.0, respectively) and cartilage volume loss at the medial tibial site (beta = -34.9 per 1 SD increase, 95% CI -49.8, -20.1). In contrast, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase, 95% CI 1.2, 2.1) and was not associated with cartilage loss. CONCLUSION The results of this study demonstrated that bone area predicted medial and lateral cartilage defect development and medial cartilage volume loss, while subchondral BMD predicted medial defect development but not cartilage loss. These associations were independent of each other, indicating there are multiple mechanisms by which subchondral bone changes may lead to cartilage damage.

Correlates of Subchondral BMD: A Cross-Sectional Study

Subchondral bone is hypothesized to be important in the development and progression of osteoarthritis (OA); however, little is known about the determinants of subchondral bone. This study describes the relationship between tibial subchondral BMD (sBMD) and anthropometric, lifestyle, and structural measures in 740 randomly selected subjects (mean age, 62 yr; range, 50–80 yr; 52% women). We measured medial tibial sBMD by DXA at two regions of interest (ROIs). We also assessed anthropometrics, vitamin D, steps per day by pedometer, joint space narrowing (JSN) and osteophytes (by X‐ray), cartilage defects, cartilage volume, and bone marrow lesions (BML; by MRI), and hip and spine BMD (by DXA). sBMD using ROI 1 was negatively associated with age and female sex and positively associated with BMI. In multivariable analysis, sBMD was positively correlated with steps per day (r = 0.08, p = 0.025), tibial osteophytes (r = 0.08, p = 0.028), JSN (r = 0.11, p < 0.01), cartilage defects (r = 0.16, p < 0.01), cartilage volume (r = 0.12, p = 0.01), BMLs (r = 0.17, p = 0.013 [tibial]; r = 0.16, p = 0.018 [femoral]), and hip and spine BMD (r = 0.36, p < 0.01 and r = 0.38, p < 0.01, respectively). Similar associations were observed using ROI 2, with vitamin D also associated with sBMD (r = 0.10, p < 0.01). In conclusion, this study identified a large number of factors associated with sBMD, of which the most novel is cartilage defects. Longitudinal studies are required to address causality.

A longitudinal study of the association between dietary factors, serum lipids, and bone marrow lesions of the knee

IntroductionBone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs.MethodsIn total, 394 older men and women (mean age, 63 years; range, 52 to 79) were measured at baseline and approximately 2.7 years later. BMLs were determined by using T2-weighted fat-saturation magnetic resonance imaging (MRI) by measuring the maximal area of the lesion. Nutrient intake (total energy, fat, carbohydrate, protein, and sugar) and serum lipids were assessed at baseline.ResultsCross-sectionally, dietary factors and lipids were not significantly associated with BMLs. Energy, carbohydrate, and sugar intake (but not fat) were positively associated with a change in BML size (β = 15.44 to 19.27 mm2 per 1 SD increase; all P < 0.05). High-density lipoprotein (HDL) cholesterol tended to be negatively associated with BML change (β = -11.66 mm2 per 1 SD increase; P = 0.088).ConclusionsEnergy, carbohydrate, and sugar intake may be risk factors for BML development and progression. HDL cholesterol seems protective against BMLs. These results suggest that macronutrients and lipids may be important in BML etiology and that dietary modification may alter BML natural history.

A pilot study of the reproducibility and validity of measuring knee subchondral bone density in the tibia

OBJECTIVE To describe the reproducibility and validity of six different measurement techniques for knee subchondral bone mineral density (sBMD). METHODS A consecutive sample of 50 male and female participants from a population-based longitudinal study had sBMD assessed using dual energy X-ray absorptiometry scans. Anthropometric, knee pain, cartilage and bone measures by magnetic resonance imaging and radiographic osteoarthritis (OA) were assessed. The six methods were defined as: (1) the midpoint of one intercondylar spine, across the tibial surface and descending 10mm; from the midpoint of the two intercondylar spines (2) the top of the spine descending 20mm, (3) 10-20mm beneath the top of the spine; from the tibial surface descending, (4) 10mm, (5) 15 mm, and (6) 20mm. RESULTS All six methods had excellent reproducibility (intra-class correlation coefficient 0.98-1.00). sBMD was higher in males (methods 2-4) and higher in those with medial tibial osteophytes (methods 1, 3 and 4). Medial tibial cartilage defects and overall cartilage defects correlated with sBMD (methods 3 and 4). Method 2, which includes the intercondylar spine, correlated with medial tibial bone size. Measuring sBMD using methods 3 and 4 produced the greatest number of associations with joint features of OA. CONCLUSIONS These preliminary results need confirmation in larger longitudinal samples but suggest that sBMD can be accurately measured and plays a role in knee OA. Methods 3 and 4 had the best concurrent validity; however, method 2 adds additional information on tibial bone size, suggesting that two measures are necessary in clinical studies.

Vitamin D deficiency in Tasmania: a whole of life perspective.

This study aims to describe the lifetime picture of vitamin D deficiency, as measured by serum 25(OH)D concentration, in Tasmania (latitude 43°S).

Physical Activity and Osteoarthritis of the Knee: Can MRI Scans Shed More Light on This Issue?

Abstract Physical activity has many health benefits; however, there has been concern that exercise may increase the risk of the development or progression of osteoarthritis (OA) of the knee. There is little doubt that injury increases the risk of OA, but the role of physical activity independent to injury is uncertain. Recently, magnetic resonance imaging has allowed an in-depth assessment of joints and relevant structural changes—this review covers the recent imaging data relevant to this area. In children and young adults, physical activity appears beneficial for knee cartilage, possibly even in structurally abnormal knees. In addition, there is consistent evidence showing aerobic and strengthening exercise improves OA symptoms later in life. However, there is limited evidence associating exercise with structural changes in later life and this lacks consistency, suggesting little or no effect. In the meantime, it appears safe to prescribe exercise in later life without major concern for structural deterioration, although caution is appropriate in those with bone marrow lesions until more information becomes available.