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Increased matrix concentrations of IGFBP-5 in cancellous bone in osteoarthritis

¹ Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust, Oswestry, Shropshire SY10 7AG, UK
² Bone and Mineral Metabolic Unit, Division of Clinical Chemistry, Faculty of Health Sciences, Linköping University Hospital, Sweden
³ Musculoskeletal Disease Center, Jerry L Pettis VA Medical Center, Loma Linda, CA, USA

Correspondence to:
Correspondence to:
Dr C A Sharp
chris.sharp{at}rjah.nhs.uk

ABSTRACT
Background: In osteoarthritis cancellous bone adapts to meet altered mechanical loading. These changes may be mediated by insulin-like growth factors (IGF-I and IGF-II), but the matrix bound binding protein, IGFBP-5 has not been investigated.

Objectives: To measure IGF-I, IGF-II, and IGFBP-5 in femoral head bone from non-OA controls and patients with OA, and to relate these to apparent density (_A) and elastic modulus (Ec).

Methods: _A, Ec, and IGF system components were measured in cancellous bone from superior and inferior regions of femoral heads from 31 patients with OA and 11 age selected controls.

Results: Ec and _A were greater (p<0.05) in the superior region of all femoral heads. In primary OA, _A was increased in the inferior region (p<0.05). IGFBP-5 was increased, about twofold, at superior and inferior regions in primary OA (1.60 and 1.54 ng/mg bone, respectively, both p<0.05) and in Paget’s disease (2.44 and 1.75 ng/mg bone, both p<0.05) compared with controls (0.73 and 0.95 ng/mg bone). In controls, inverse correlations between IGFBP-5 and both _A and Ec at superior (r_s = –0.64 and –0.73, both p<0.05) and inferior regions (r_s = –0.72, p<0.05 and –0.24 (NS)) were seen, but these were lost in OA.

Conclusions: IGFBP-5 may modulate cancellous bone formation by negative feedback. In end stage OA this is disrupted, but has little influence on material properties.

Abbreviations: Ec, elastic modulus; IGF, insulin-like growth factor; IGFBP-5, insulin-like growth factor binding protein-5, OA, osteoarthritis; _A, apparent density

Keywords: osteoarthritis; insulin-like growth factors; bone matrix; Paget’s disease

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