The relationship and interactions between sun exposure, skin phenotype and musculoskeletal health in older adults
Creators: name: Thompson, Michael
Publisher: name: University Of Tasmania
Year: 2023

description: Fragility fractures are a common and costly consequence of osteoporosis that impair quality of life and are associated with increased mortality. Vitamin D deficiency is a common, modifiable determinant of musculoskeletal health. In many parts of the world sun exposure is the major determinant of vitamin D status. Skin phenotype is known to modify vitamin D status and the toxicities of sun exposure both acutely and across the lifespan, but the prevailing data are subject to significant limitations. This Thesis therefore investigated the relationship and interactions between sun exposure, skin phenotype and musculoskeletal health in older adults.Data from a population-based prospective cohort study of 1,099 community-dwelling adults aged 50–80 years (51% women; mean age 62 years) followed up at baseline, 2.5, 5, and 10 years were analysed. Skin phenotype was quantified using spectrophotometry of a non-sun exposed site (the upper inner arm) to determine constitutive melanin density and by self-report questionnaire on ability to tan, propensity to sunburn and hair colour to determine skin photosensitivity. Sun exposure, smoking status and the prevalence, incidence and number of symptomatic fractures were assessed by questionnaire. Bone mineral density (BMD) and vertebral deformity were quantified using dual-energy X-ray absorptiometry, falls risk by the short form Physiological Profile Assessment, ambulatory activity by pedometer and bone microarchitecture by high resolution peripheral quantitative CT. Serum 25-hydroxyvitamin D (25(OH)D) concentration was measured using radioimmunoassay and &lt;50 nmol/L was considered deficient. Vitamin D supplement use was assessed at clinic review. Nonmelanoma skin cancer (NMSC) diagnosis was quantified by self-report (Chapters 4, 5 &amp; 6) and histopathologically-confirmed NMSC diagnosis was established by linkage with the Tasmanian Cancer Registry (Chapter 7).The first and second studies examined the association between spectrophotometrically-determined constitutive melanin density, osteoporotic fracture risk factors and outcomes in older Caucasian adults. Data from the first study supported a model of higher constitutive melanin density underpinning a less photosensitive skin phenotype, resulting in greater sun exposure with fewer sequelae and consequently a higher 25(OH)D and total body BMD. However, the second study demonstrated that higher constitutive melanin density was paradoxically associated with more prevalent and short-term incident fractures and that there was no association with long-term incident fractures. This suggested melanin density was either (1) acting as a surrogate marker for an unmeasured fracture risk factor and did not have a strong independent influence on fracture outcomes or (2) the relationship between melanin density and fracture changes with time.The third study investigated whether skin photosensitivity modulates sun exposure behaviours, consequent vitamin D status and skeletal health outcomes independent of constitutive melanin density. This analysis demonstrated that cutaneous photosensitivity, particularly ability to tan and resistance to sunburn, was associated with sun exposure behaviours, cutaneous sequelae and, consequently, 25(OH)D and BMD in older Caucasian adults independent of constitutive melanin density. However, there was again no consistent association with fracture outcomes, suggesting that environmental factors are at least as important as skin phenotype in determining fracture outcomes.The fourth study examined the relationship between histopathologically-determined NMSC, fracture risk factors and outcomes. This analysis confirmed previous work and demonstrated that NMSC, a biomarker of cumulative lifetime sun exposure, was associated with reduced risk of later life fragility fracture. Further analysis demonstrated the protective association was potentially mediated by modifiable fracture risk factors associated with an outdoor lifestyle, including higher 25(OH)D and BMD and improved bone microarchitecture, specifically reduced cortical porosity and higher cortical volumetric BMD. This study emphasised the contribution of modifiable fracture risk factors, rather than nonmodifiable factors (skin phenotype), to later life fragility fracture risk, suggesting an opportunity to influence the population burden of disease.The final study investigated the longitudinal change in cohort 25(OH)D concentration and the association of longitudinal vitamin D status with change in BMD. This analysis demonstrated that cohort 25(OH)D concentration increased due to a combination of increased sun exposure and supplement use. Maintaining longitudinal vitamin D sufficiency was associated with less BMD loss over 10 years. Participants who attained vitamin D sufficiency had similar BMD outcomes compared to participants who were always sufficient, suggesting the excess BMD loss associated with vitamin D deficiency may be reversible when deficiency is corrected. This study demonstrated that it is possible to modify vitamin D stores on a cohort level over an extended period of time through a combination of interventions and that this is associated with a beneficial impact on BMD.In conclusion, skin phenotype modified sun exposure behaviour, cutaneous sequelae of sun exposure and fracture risk factors, but did not have a strong independent influence on fracture outcomes. It is likely that modifiable fracture risk factors associated with an outdoor lifestyle contribute to the protective relationship between NMSC and fragility fractures later in life. These data suggest an opportunity to modify the population burden of later life fragility fractures through interventions aimed at maintaining vitamin D sufficiency throughout life. Translating this into practice will require a multifaceted approach including review of Australia’s sun exposure guidelines, food fortification policies and legislation and a targeted test and treatment approach in clinical practice.