Determinants, correlates and modifiers of musculoskeletal pain

Arthritis is the most common cause of chronic pain in older people. Pain is a priority for patients and an important clinical symptom, as it predicts service use, disability and joint replacements. Treatment options remain palliative, and effect sizes suboptimal. This thesis investigates correlates, determinants and modifiers of musculoskeletal pain. The first study utilised data from TASOAC, a population of community dwelling older adults aged 50‚Äö-80 randomly selected from the electoral roll and followed for five years to describe associations between aspects of osteoarthritis (OA) and quality of life. This study identified that pain at all joint sites is common in older adults, is stable over time, and is the strongest musculoskeletal correlate of quality of life. Pain also mediates the association between diagnosed OA and quality of life. In the second study, in this same population, associations between serum vitamin D (25‚Äö-OHD) and change in knee and hip pain were investigated. Moderate (but not mild) vitamin D deficiency independently predicted incident or worsening in knee pain over 5 years and possibly hip pain over 2.4 years. Therefore correcting moderate vitamin deficiency may attenuate worsening of knee or hip pain in elderly persons but supplementing people with a higher 25‚Äö-OHD level is unlikely to be effective. In the third and fourth studies, potential modifiers of musculoskeletal pain were investigated. In the former, efficacy of thrice daily topical 4Jointz utilizing Acteev technology (a combination of a standardized comfrey extract and pharmaceutical grade tannic acid, 3.5 g/day) vs placebo was assessed on osteoarthritic outcomes over 12 weeks in participants aged ‚Äöv¢‚Ä¢50 years with clinically defined knee OA, pain on most days, and VAS pain intensity ‚Äöv¢‚Ä¢40mm (n=133). Topical treatment using 4Jointz reduced pain compared to placebo (VAS -9.9 mm, p=0.034; KOOS pain scale +5.7, p = 0.047), but had no effect on inflammation or cartilage breakdown over 12 weeks of treatment. In the fourth study, efficacy of zoledronic acid (ZA: 5mg/100ml) vs placebo over 12 months in participants aged ‚Äöv¢‚Ä¢50 years with clinically defined knee OA, pain on most days, VAS pain intensity ‚Äöv¢‚Ä¢40mm and a bone marrow lesion visible on T2-weighted MR images (n=59) was assessed. Treatment with ZA (compared to placebo) improved VAS pain scores after six months (-14.5 mm, p=0.04) but not after three or twelve months. ZA treatment reduced total BML area compared to placebo after six months (-175.7 mm\\(^2\\), p=0.024); with a trend after twelve months (-146.5 mm\\(^2\\), p=0.095). This provided the first evidence of a treatment to modify structural progression in OA. In conclusion, this series of studies indicate that pain is a strong and stable musculoskeletal correlate of quality of life over time, vitamin D is a determinant of musculoskeletal pain, and treatment with 4Jointz and ZA are both effective in reducing pain. Additionally, ZA modifies structural progression by reducing total BML area; therefore, a lesion‚Äö-specific approach to treatment of osteoarthritis pain is feasible. Future work should include targeting cognitive correlates of pain, clinical trials of vitamin D supplementation, and clinical trials of ZA to investigate effects on cartilage.