Osteophytes, Enthesophytes, and High Bone Mass: A Bone‐Forming Triad With Potential Relevance in Osteoarthritis

Hardcastle, Sarah; Dieppe, Paul; Gregson, Celia L; Arden, N K; Spector, Tim D.; Hart, Deborah; Edwards, Mark H.; Dennison, Elaine; Cooper, Cyrus; Williams, Martin; Smith, George Davey; Tobias, Jonathan H

doi:10.1002/art.38729

Cited by 48 publications

(37 citation statements)

References 45 publications

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“…This is supported by the additional observation that HBM individuals also have a greater prevalence and severity of radiographic pelvic enthesophytes (bony spurs at tendon and ligament insertions). 61 Although the genetic basis for increased BMD in the majority of these HBM cases remains to be determined, and is the subject of ongoing studies, a genome-wide association analysis has shown overrepresentation of single-nucleotide polymorphisms (SNPs) that were previously shown to be associated with BMD variation in the general population. 62 It is hoped that whole-exome sequencing in this unique group, currently underway, could identify novel pathways with a role in both OA and bone mass regulation.…”

Section: Oa In High Bone Mass Individuals: a Novel Approachmentioning

confidence: 99%

Osteoarthritis and bone mineral density: are strong bones bad for joints?

et al. 2015

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Osteoarthritis (OA) is a common and disabling joint disorder affecting millions of people worldwide. In OA, pathological changes are seen in all of the joint tissues including bone. Although both cross-sectional and longitudinal epidemiological studies have consistently demonstrated an association between higher bone mineral density (BMD) and OA, suggesting that increased BMD is a risk factor for OA, the mechanisms underlying this observation remain unclear. Recently, novel approaches to examining the BMD-OA relationship have included studying the disease in individuals with extreme high bone mass, and analyses searching for genetic variants associated with both BMD variation and OA, suggesting possible pleiotropic effects on bone mass and OA risk. These studies have yielded valuable insights into potentially relevant pathways that might one day be exploited therapeutically. Although animal models have suggested that drugs reducing bone turnover (antiresorptives) may retard OA progression, it remains to be seen whether this approach will prove to be useful in human OA. Identifying individuals with a phenotype of OA predominantly driven by increased bone formation could help improve the overall response to these treatments. This review aims to summarise current knowledge regarding the complex relationship between BMD and OA.

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Section: Oa In High Bone Mass Individuals: a Novel Approachmentioning

confidence: 99%

Osteoarthritis and bone mineral density: are strong bones bad for joints?

et al. 2015

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“…These osteoarthritis hips exerted a bony phenotype with increased osteophytes and bone sclerosis. This study [10] suggests that this population with a 'bone-forming' tendency are at higher risk of developing osteoarthritis. Conversely, results from the Rotterdam Study suggest that a subtype of patients with an atrophic osteoarthritis phenotype (as defined by absence of osteophyte) are at higher risk of hip fracture, independently from systemic BMD [11].…”

Section: Bone Mineral Densitymentioning

confidence: 85%

Subchondral bone and osteoarthritis

Funck‐Brentano

Cohen‐Solal

2015

Current Opinion in Rheumatology

103

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The involvement of bone in osteoarthritis has long been thought to be secondary to cartilage damage as an adaptation of the joint. Recent clinical studies with MRI have demonstrated that bone changes could be observed in early stages of the disease, even preceding cartilage lesions. Moreover, there is clear evidence of an association between subchondral bone mineral density and osteoarthritis. The level of bone remodeling plays a critical role under mechanical loading conditions as demonstrated by consistent experimental studies. Yet new clinical biomarkers are being developed to assess the bone phenotype of osteoarthritic patients. This stratification strategy is likely to better identify groups of patients who would benefit from bone-acting drugs to decrease disease progression and improve pain and disability.

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“…Further characterisation of knee OA revealed a similar, osteophyte predominant, radiographic OA phenotype [10]. Additional evidence of a ‘bone-forming’ tendency is supported by a greater prevalence and severity of radiographic pelvic enthesophytes (bony spurs at tendon/ligament insertions) seen in HBM individuals, compared with family controls [11].…”

Section: Introductionmentioning

confidence: 86%

High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index

Gregson

Hardcastle

Murphy

et al. 2017

Bone

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ObjectivesHigh Bone Mass (HBM) is associated with (a) radiographic knee osteoarthritis (OA), partly mediated by increased BMI, and (b) pelvic enthesophytes and hip osteophytes, suggestive of a bone-forming phenotype. We aimed to establish whether HBM is associated with radiographic features of OA in non-weight-bearing (hand) joints, and whether such OA demonstrates a bone-forming phenotype.MethodsHBM cases (BMD Z-scores ≥ + 3.2) were compared with family controls. A blinded assessor graded all PA hand radiographs for: osteophytes (0–3), joint space narrowing (JSN) (0–3), subchondral sclerosis (0–1), at the index Distal Interphalangeal Joint (DIPJ) and 1st Carpometacarpal Joint (CMCJ), using an established atlas. Analyses used a random effects logistic regression model, adjusting a priori for age and gender. Mediating roles of BMI and bone turnover markers (BTMs) were explored by further adjustment.Results314 HBM cases (mean age 61.1 years, 74% female) and 183 controls (54.3 years, 46% female) were included. Osteophytes (grade ≥ 1) were more common in HBM (DIPJ: 67% vs. 45%, CMCJ: 69% vs. 50%), with adjusted OR [95% CI] 1.82 [1.11, 2.97], p = 0.017 and 1.89 [1.19, 3.01], p = 0.007 respectively; no differences were seen in JSN. Further adjustment for BMI failed to attenuate ORs for osteophytes in HBM cases vs. controls; DIPJ 1.72 [1.05, 2.83], p = 0.032, CMCJ 1.76 [1.00, 3.06], p = 0.049. Adjustment for BTMs (concentrations lower amongst HBM cases) did not attenuate ORs.ConclusionsHBM is positively associated with OA in non-weight-bearing joints, independent of BMI. HBM-associated OA is characterised by osteophytes, consistent with a bone-forming phenotype, rather than JSN reflecting cartilage loss. Systemic factors (e.g. genetic architecture) which govern HBM may also increase bone-forming OA risk.

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Osteophytes, Enthesophytes, and High Bone Mass: A Bone‐Forming Triad With Potential Relevance in Osteoarthritis

Cited by 48 publications

References 45 publications

Osteoarthritis and bone mineral density: are strong bones bad for joints?

Osteoarthritis and bone mineral density: are strong bones bad for joints?

Subchondral bone and osteoarthritis

High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index

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