The opinions expressed by correspondents in this column are not endorsed by the editors or The Royal Australian College of General Practitioners.
Link between brain and bone
Congratulations Mughal and colleagues for the excellent study on the underestimated crosstalk between bone and brain in the orthogeriatric setting (AJGP January–February 2019).1 In the introduction, the authors named the direct costs related to osteoporosis in Australia at $1.9 billion per year. However, this amount was estimated for the financial year 2000–01. In 2017, the annual total direct healthcare system cost of osteoporosis in Australia was $3.44 billion.2 General practitioners (GPs) should know these current costs. And considering that the total annual direct cost of dementia is expected to reach $9.6 billion in Australia in 2019 (plus $5.9 billion in indirect costs of dementia),3 the relevant bidirectional interplay between osteoporosis and dementia as well as the implications for GPs identified by the authors take an even greater significance.
The following shared/intermediate risk factors were evaluated for both common degenerative diseases in the elderly population: ageing, female sex, lack of physical activity and mobility, falls, genetic susceptibility factors (eg apolipoprotein E4 allele – a major cholesterol carrier), lower vitamin K levels, vitamin D/calcium deficiencies and oestrogen or androgen deficiency.4,5 As a potential driving mechanism for bone loss in Alzheimer’s disease pathogenesis, a systemic dysfunction of signalling in the complex canonical Wnt (wingless-type mouse mammary tumour virus integration site)/beta-catenin pathway has also been discussed in recent years. The complex Wnt signalling plays a fundamental part in the regulation of cellular function in most tissues – including the maintenance of homeostasis of the bone and brain (eg facilitating bone formation in bone tissues, promoting synaptogenesis and neurogenesis in the brain).4,5 Furthermore, the exercise-induced myokine irisin and its membrane-bound precursor protein, fibronectin type III domain-containing protein 5, appear to have an important interconnected mediator function in age-related bone loss and Alzheimer’s disease–associated neurodegeneration.4 Some examples: irisin stimulates new bone formation, enhances brain-derived neurotrophic factor gene synthesis and release, protects the nervous system by facilitating hippocampal proliferation and suppressing amyloid-beta aggregation, and stimulates Wnt/beta-catenin signalling through downregulation of sclerotin (a Wnt pathway inhibitor).4,6,7
Among the pathophysiological brain–bone interactions, a recent Australian review by Yuan et al also discussed bone-related modulators that may influence the progression of Alzheimer’s disease: bone-derived cellular secretory proteins including osteocalcin, osteopontin and sclerostin, as well as bone marrow–derived cells including microglia-like cells, hematopoietic stem cells and mesenchymal stem cells.5 Further studies are urgently needed to bring more scientific evidence into the complexities of this age-related brain–bone comorbidity and – hopefully as soon as possible – more prevention into clinical practice.4–7
Martin Hofmeister
Consumer Centre of the German Federal State of Bavaria,
Department Food and Nutrition, Germany
References
- Mughal N, Inderjeeth AJ, Inderjeeth CA. Osteoporosis in patients with dementia is associated with high morbidity and mortality: Findings from a single orthogeriatric unit. Aust J Gen Pract 2019;48(1–2):53–58.
- Tatangelo G, Watts J, Lim K, et al. The cost of osteoporosis, osteopenia, and associated fractures in Australia in 2017. J Bone Miner Res 2019;34(4):616–25. doi: 10.1002/jbmr.3640.
- Brown L, Hansnata E, La HA. Economic cost of Dementia in Australia 2016–2056. ACT: IGPA, University of Canberra, 2017.
- Frame G, Bretland KA, Dengler-Crish CM. Mechanistic complexities of bone loss in Alzheimer’s disease: A review. Connect Tissue Res 2019;Jun 11:1–15. doi: 10.1080/03008207.2019.1624734.
- Yuan J, Meloni BP, Shi T, et al. The potential influence of bone-derived modulators on the progression of Alzheimer’s disease. J Alzheimers Dis 2019;69(1):59–70. doi: 10.3233/JAD-181249.
- Colaianni G, Sanesi L, Storlino G, Brunetti G, Colucci S, Grano M. Irisin and bone: From preclinical studies to the evaluation of its circulating levels in different populations of human subjects. Cells 2019;8(5):E451. doi: 10.3390/cells8050451.
- Jin Y, Sumsuzzman DM, Choi J, Kang H, Lee SR, Hong Y. Molecular and functional interaction of the myokine irisin with physical exercise and Alzheimer’s disease. Molecules 2018;23(12):E3229. doi: 10.3390/molecules23123229.
Retraction
Dixon AJ, Steinman HK, Nirenberg A, Anderson S, Dixon JB. Cutaneous melanoma: Latest developments. Aust J Gen Pract 2019;48(6):349–53.
Dixon AJ, Steinman HK, Nirenberg A, Dixon ZL, Anderson S, Dixon JB. Management of invasive melanoma. Aust J Gen Pract 2019;48(6):368–72.
These articles have been retracted by the Australian Journal of General Practice for the following reason: A Letter to the Editor from Professor John Thompson, Melanoma Institute, reported that these articles contained a large number of factual errors that undermined the reliability of the overall articles. After consultation with our expert independent advisory panel, we have decided to retract both articles. Pending publication of an updated version, we refer readers to the published Australian guidelines for clinical practice for the diagnosis and management of melanoma (https://wiki.cancer.org.au/australia/Guidelines:Melanoma).