Objective

Nerve growth factor (NGF) is a key regulator of nociceptive pain and thus appears to be an interesting target molecule for an innovative class of analgesic medication. We set out to review the principles of neurogenic inflammation and results of anti-NGF regimens in animal studies as well as clinical trials with patients with back pain and osteoarthritis (OA).

Design

We searched using Google Scholar Search and Pubmed as well as through conference reports for articles and abstracts related to NGF and clinical trials using anti-NGF regimens. We report on efficacy findings and adverse events (AEs) related to these agents in this review.

Results

We identified five full articles and eight abstract reports relating to anti-NGF agents studied for use in back pain and in OA.

Conclusions

Anti-NGF agents either alone or in combination with non-steroidal anti-inflammatory agents (NSAIDs) were more efficacious for the treatment of pain in a number of trials of knee and hip pain compared to NSAIDs alone. However, adverse effects that included rapidly progressive OA and joint replacement were more common in patients treated with anti-NGF and NSAIDs than either treatment alone. Anti-NGF treatment related neurologic symptoms including paresthesias, and potentially other types of adverse effects were usually transient but warrant additional investigation.

Both epidemiologic and clinical research continues to be performed in osteoarthritis (OA). While epidemiologic studies identify risk factors for incident and progressive disease, clinical studies explore the role of both non-pharmacologic and pharmacologic treatments, including oral and intra-articular therapies. We performed a systematic review of the literature using PubMed for the time period between April 1, 2015 to February 22, 2016. Selected publications in the areas of both epidemiology and treatment are reviewed in this article.

Objective

Lateral tibiofemoral osteoarthritis (OA) is overall less common than medial tibiofemoral OA, but it is more prevalent in women. This may be explained by sex differences in hip and pelvic geometry. The aim of this study is to explore sex differences in hip and pelvic geometry and determine if such parameters are associated with the presence of compartment-specific knee OA.

Methods

This case-control study reports on 1,328 hips/knees from 664 participants and is an ancillary to the Multicenter Osteoarthritis Study (MOST). Of the 1,328 knees, 219 had lateral OA, 260 medial OA, and 849 no OA. Hip and pelvic measurements were taken from full-limb radiographs on the ipsilateral side of the knee of interest. After adjusting for covariates, means were compared between sexes and also between knees with medial and lateral OA vs no OA using separate regression models.

Results

Women were shown to have a reduced femoral offset (FO) (mean 40.9 mm vs 45.9 mm; P = 0.001) and more valgus neck-shaft angle (mean 128.4° vs 125.9°; P < 0.001) compared to men. Compared to those with no OA, knees with lateral OA were associated with a reduced FO (P = 0.012), increased height of hip centre (HHC) (P = 0.003), more valgus neck-shaft angle (P = 0.042), and increased abductor angle (P = 0.031). Knees with medial OA were associated with a more varus neck-shaft angle (P = 0.043) and a decreased abductor angle (P = 0.003).

Conclusion

These data suggest anatomical variations at the hip and pelvis are associated with compartment-specific knee OA and may help to explain sex differences in patterns of knee OA.

Objective

This study examined the association of proximal femur shape with ipsilateral medial and lateral compartment knee osteoarthritis (OA).

Design

Radiographs were obtained from the NIH-funded Osteoarthritis Initiative (OAI). Cases of isolated radiographic lateral compartment knee OA were defined on baseline radiographs as Kellgren/Lawrence (K/L) Grade ≥ 2 and joint space narrowing (JSN) > 0 in the lateral compartment and JSN = 0 in the medial compartment; isolated medial compartment knee OA had K/L ≥ 2 and JSN > 0 medially with JSN = 0 in the lateral compartment. Controls had K/L < 2 and JSN = 0 in both compartments. Controls were frequency matched to cases by sex and 10-year age intervals. We characterized the shape of the proximal femurs on radiographs using Active Shape Modeling (ASM) and determined the association of proximal femur shape with knee OA using logistic regression.

Results

There were 168 lateral compartment knee OA cases (mean body mass index (BMI) 29.72 ± 5.26), 169 medial compartment knee OA cases (mean BMI 29.68 ± 4.83) and 168 controls (mean BMI 26.87 ± 4.2). Thirteen modes were derived for femur shape which described 95.5% of the total variance in proximal femur shape in the population. Modes 6, 8 and 12 were associated with prevalent lateral compartment knee OA. Medial compartment knee OA was associated with proximal femur modes 1, 5, 8, and 12.

Conclusions

Prevalent lateral and medial compartment knee OA are associated with different ipsilateral proximal femur shapes. Additional studies are needed to better define how the shape of the proximal femur influences compartment-specific knee OA.

Objective

We evaluated the association of parity to both risk of knee replacement (KR) and knee osteoarthritis (OA).

Design

The NIH-funded Multicenter Osteoarthritis Study (MOST) is a longitudinal observational study of persons age 50-79 years with either symptomatic knee OA or at elevated risk of disease. Baseline and 30-month knee radiographic OA (ROA) was defined as Kellgren/Lawrence (K/L) grade ≥2 or KR. Women were grouped based by number of births: 0; 1 (reference group); 2; 3; 4; and 5 or more. We examined the relation of parity to the incidence over 30 months of ROA and KR using a Poisson regression model. Generalized estimating equations (GEE) were used to control for correlation between two knees within a subject. We adjusted for age, BMI, race, education, occupation, baseline estrogen use, clinical site, injury, and for KR analyses WOMAC pain and use of pain medication.

Results

Among 1618 women who reported parity information, mean age was 62.6 years, mean BMI 30.7 kg/m(2), mean WOMAC pain subscale score 3.7 at baseline. There were 115 KRs and 134 cases of incident knee ROA over 30 months. The relative risk of incident KR was 2.7 times as high (95% CI: 1.0, 7.3) and relative risk of incident knee ROA was 2.6 times as high (95% CI: 1.2, 5.3) among women with five to 12 children compared with those with one birth.

Conclusion

Parity in women at risk for OA is associated with both incident ROA and KR, particularly for those with more than four children.

Objective

Isolated lateral compartment tibiofemoral radiographic osteoarthritis (IL-ROA) is an understudied form of knee osteoarthritis (OA). The objective of the present study was to characterize Magnetic Resonance Imaging (MRI) abnormalities and MR-T2 relaxation time measurements associated with IL-ROA and with isolated medial compartment ROA (IM-ROA) compared with knees without OA.

Method

200 case subjects with IL-ROA (Kellgren/Lawrence (K/L) grade≥2 and joint space narrowing (JSN) > 0 in the lateral compartment but JSN = 0 in the medial compartment) were randomly selected from the Osteoarthritis Initiative baseline visit. 200 cases with IM-ROA and 200 controls were frequency matched to the IL-ROA cases. Cases and controls were analyzed for odds of having a subregion with >10% cartilage area affected, with ≥25% bone marrow lesions (BML), with meniscal tear or maceration, and for association with cartilage T2 values.

Results

IL-ROA was more strongly associated with ipsilateral MRI knee pathologies than IM-ROA (IL-ROA: OR = 135.2 for size of cartilage lesion, 95% CI 42.7-427.4; OR = 145.4 for large size BML, 95% CI 41.5-509.5; OR = 176 for meniscal tears, 95% CI 59.8-517.7; IM-ROA: OR = 28.4 for size of cartilage lesion, 95% CI 14.7-54.7; OR = 38.1 for size of BML, 95% CI 12.7-114; OR = 37.0 for meniscal tears, 95% CI 12-113.6). Cartilage T2 values were higher in both tibial and medial femoral compartments in IL-ROA, but in IM-ROA were only significantly different from controls in the medial femur.

Conclusion

IL-ROA knees show a greater prevalence and severity of MRI lesions and higher cartilage T2 values than IM-ROA knees compared with controls.