Individuals With High Bone Mass Have Increased Progression of Radiographic and Clinical Features of Knee Osteoarthritis

April E. Hartley; Sarah A. Hardcastle; Lavinia Paternoster; Eugene McCloskey; Kenneth E. S. Poole; Muhammad K. Javaid; Mo  Aye; Katie Moss; Raquel Granell; Jenny Gregory; Martin Williams; Jon H. Tobias; Celia L. Gregson

doi:10.1016/j.joca.2020.03.020

Individuals With High Bone Mass Have Increased Progression of Radiographic and Clinical Features of Knee Osteoarthritis

April E. Hartley^*, Sarah A. Hardcastle, Lavinia Paternoster, Eugene McCloskey, Kenneth E. S. Poole, Muhammad K. Javaid, Mo Aye, Katie Moss, Raquel Granell, Jenny Gregory, Martin Williams, Jon H. Tobias, Celia L. Gregson

^*Corresponding author for this work

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Abstract

Objective: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. Design: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score>+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. Results: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean(SD) age was 58(12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR=1.55[0.56,4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45[0.01,0.89] and 0.15[0.01,0.29], respectively). HBM individuals had higher WOMAC knee pain scores (β=7.42[1.17,13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. Conclusions: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.

Original language	English
Pages (from-to)	1180-1190
Number of pages	11
Journal	Osteoarthritis and Cartilage
Volume	28
Issue number	9
Early online date	14 May 2020
DOIs	https://doi.org/10.1016/j.joca.2020.03.020
Publication status	Published - Sept 2020

Bibliographical note

Acknowledgements:
We would like to thank all our HBM study participants and the staff at the University of Bristol and our collaborating centres: Addenbrooke’s Wellcome Trust Clinical Research Facility, NIHR Bone Biomedical Research Unit in Sheffield, the Centre for Metabolic Bone Disease in Hull, Southmead Hospital in Bristol, Nuffield Orthopaedic Centre in Oxford, the Royal National Hospital for Rheumatic Diseases in Bath and St George’s Hospital in London.

Role of the funding source:
The HBM study was supported by The Wellcome Trust (080280/Z/06/Z), the National Institute for Health Research Clinical Research Network (portfolio no. 5163) and Versus Arthritis (ref 20000). AH is funded by the Wellcome Trust (grant ref 20378/Z/16/Z). Follow-up imaging at the Hull site was funded by OSPREY (OSteoPorosis Research in East Yorkshire). AH, LP, JHT and CLG work in, or are affiliated with, a University of Bristol and MRC funded unit (MC_UU_00011/1).

Keywords

osteoarthritis
progression
high bone mass
BMD
WOMAC
health-related quality of life
Progression
Health-related quality of life
High bone mass
Osteoarthritis
STANDARDIZATION
INCIDENT
INCREASED PREVALENCE
RISK
HIP
REPLACEMENT
WOMEN
MINERAL DENSITY
ELDERLY-MEN
ASSOCIATION

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Hartley, A. E., Hardcastle, S. A., Paternoster, L., McCloskey, E., Poole, K. E. S., Javaid, M. K., Aye, M., Moss, K., Granell, R., Gregory, J., Williams, M., Tobias, J. H., & Gregson, C. L. (2020). Individuals With High Bone Mass Have Increased Progression of Radiographic and Clinical Features of Knee Osteoarthritis. Osteoarthritis and Cartilage, 28(9), 1180-1190. https://doi.org/10.1016/j.joca.2020.03.020

Hartley, AE, Hardcastle, SA, Paternoster, L, McCloskey, E, Poole, KES, Javaid, MK, Aye, M, Moss, K, Granell, R, Gregory, J, Williams, M, Tobias, JH & Gregson, CL 2020, 'Individuals With High Bone Mass Have Increased Progression of Radiographic and Clinical Features of Knee Osteoarthritis', Osteoarthritis and Cartilage, vol. 28, no. 9, pp. 1180-1190. https://doi.org/10.1016/j.joca.2020.03.020

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title = "Individuals With High Bone Mass Have Increased Progression of Radiographic and Clinical Features of Knee Osteoarthritis",

abstract = "Objective: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. Design: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score>+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. Results: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean(SD) age was 58(12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR=1.55[0.56,4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45[0.01,0.89] and 0.15[0.01,0.29], respectively). HBM individuals had higher WOMAC knee pain scores (β=7.42[1.17,13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. Conclusions: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.",

keywords = "osteoarthritis, progression, high bone mass, BMD, WOMAC, health-related quality of life, Progression, Health-related quality of life, High bone mass, Osteoarthritis, STANDARDIZATION, INCIDENT, INCREASED PREVALENCE, RISK, HIP, REPLACEMENT, WOMEN, MINERAL DENSITY, ELDERLY-MEN, ASSOCIATION",

author = "Hartley, {April E.} and Hardcastle, {Sarah A.} and Lavinia Paternoster and Eugene McCloskey and Poole, {Kenneth E. S.} and Javaid, {Muhammad K.} and Mo Aye and Katie Moss and Raquel Granell and Jenny Gregory and Martin Williams and Tobias, {Jon H.} and Gregson, {Celia L.}",

note = "Acknowledgements: We would like to thank all our HBM study participants and the staff at the University of Bristol and our collaborating centres: Addenbrooke{\textquoteright}s Wellcome Trust Clinical Research Facility, NIHR Bone Biomedical Research Unit in Sheffield, the Centre for Metabolic Bone Disease in Hull, Southmead Hospital in Bristol, Nuffield Orthopaedic Centre in Oxford, the Royal National Hospital for Rheumatic Diseases in Bath and St George{\textquoteright}s Hospital in London. Role of the funding source: The HBM study was supported by The Wellcome Trust (080280/Z/06/Z), the National Institute for Health Research Clinical Research Network (portfolio no. 5163) and Versus Arthritis (ref 20000). AH is funded by the Wellcome Trust (grant ref 20378/Z/16/Z). Follow-up imaging at the Hull site was funded by OSPREY (OSteoPorosis Research in East Yorkshire). AH, LP, JHT and CLG work in, or are affiliated with, a University of Bristol and MRC funded unit (MC_UU_00011/1).",

year = "2020",

month = sep,

doi = "10.1016/j.joca.2020.03.020",

language = "English",

volume = "28",

pages = "1180--1190",

journal = "Osteoarthritis and Cartilage",

issn = "1063-4584",

publisher = "ELSEVIER APPL SCI PUBL LTD",

number = "9",

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TY - JOUR

T1 - Individuals With High Bone Mass Have Increased Progression of Radiographic and Clinical Features of Knee Osteoarthritis

AU - Hartley, April E.

AU - Hardcastle, Sarah A.

AU - Paternoster, Lavinia

AU - McCloskey, Eugene

AU - Poole, Kenneth E. S.

AU - Javaid, Muhammad K.

AU - Aye, Mo

AU - Moss, Katie

AU - Granell, Raquel

AU - Gregory, Jenny

AU - Williams, Martin

AU - Tobias, Jon H.

AU - Gregson, Celia L.

N1 - Acknowledgements: We would like to thank all our HBM study participants and the staff at the University of Bristol and our collaborating centres: Addenbrooke’s Wellcome Trust Clinical Research Facility, NIHR Bone Biomedical Research Unit in Sheffield, the Centre for Metabolic Bone Disease in Hull, Southmead Hospital in Bristol, Nuffield Orthopaedic Centre in Oxford, the Royal National Hospital for Rheumatic Diseases in Bath and St George’s Hospital in London. Role of the funding source: The HBM study was supported by The Wellcome Trust (080280/Z/06/Z), the National Institute for Health Research Clinical Research Network (portfolio no. 5163) and Versus Arthritis (ref 20000). AH is funded by the Wellcome Trust (grant ref 20378/Z/16/Z). Follow-up imaging at the Hull site was funded by OSPREY (OSteoPorosis Research in East Yorkshire). AH, LP, JHT and CLG work in, or are affiliated with, a University of Bristol and MRC funded unit (MC_UU_00011/1).

PY - 2020/9

Y1 - 2020/9

N2 - Objective: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. Design: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score>+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. Results: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean(SD) age was 58(12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR=1.55[0.56,4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45[0.01,0.89] and 0.15[0.01,0.29], respectively). HBM individuals had higher WOMAC knee pain scores (β=7.42[1.17,13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. Conclusions: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.

AB - Objective: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. Design: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score>+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. Results: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean(SD) age was 58(12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR=1.55[0.56,4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45[0.01,0.89] and 0.15[0.01,0.29], respectively). HBM individuals had higher WOMAC knee pain scores (β=7.42[1.17,13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. Conclusions: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.

KW - osteoarthritis

KW - progression

KW - high bone mass

KW - BMD

KW - WOMAC

KW - health-related quality of life

KW - Progression

KW - Health-related quality of life

KW - High bone mass

KW - Osteoarthritis

KW - STANDARDIZATION

KW - INCIDENT

KW - INCREASED PREVALENCE

KW - RISK

KW - HIP

KW - REPLACEMENT

KW - WOMEN

KW - MINERAL DENSITY

KW - ELDERLY-MEN

KW - ASSOCIATION

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U2 - 10.1016/j.joca.2020.03.020

DO - 10.1016/j.joca.2020.03.020

M3 - Article

C2 - 32417557

SN - 1063-4584

VL - 28

SP - 1180

EP - 1190

JO - Osteoarthritis and Cartilage

JF - Osteoarthritis and Cartilage

IS - 9

ER -

Individuals With High Bone Mass Have Increased Progression of Radiographic and Clinical Features of Knee Osteoarthritis

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