Bone Abstracts

Genetic factors are recognised to play a role in the pathogenesis of osteoporosis and twin studies have indicated that the heritability of bone mineral density (BMD) may be as high as 85% at some skeletal sites. The heritability of fracture is much lower however; for hip fracture the heritability in people under 65 years is around 68% but this falls to a negligible level of about 3% above the age of 80. Genome wide association studies (GWAS) have shown that in general, regulation of BMD and quantitative ultrasound properties of bone is determined by hundreds of genetic variants each with a small effect. A recent GWAS study in Biobank UK (BBUK) reported that when these variants were combined, the heritability of total hip BMD was 31.9% and spine BMD was 36.3%, but they did not predict fracture appreciably. Occasionally susceptibility to osteoporosis can be determined by pathogenic variants with large effect. Variants in genes including WNT1 COL1A1, COL1A2, LRP5 BMP1 and PLS3 appear to play a role in about 40-50% of individuals with early onset idiopathic osteoporosis and in about 5-10% of individuals with pregnancy and lactation associated osteoporosis (PLO). In routine clinical practice, there isnt a role for routine genetic testing in most people with osteoporosis, but this should be considered in patients with PLO and those aged 40 and under with early onset idiopathic osteoporosis. There is little information on whether or not these individuals should be treated differently, with the exception of those with variants in COL1A1 and COL1A2, as this indicates that the diagnosis is not osteoporosis but osteogenesis imperfecta. Recent trials in this condition have shown that bisphosphonates, teriparatide and setrusumab do not prevent fractures even though they increase BMD. If pathogenic variants are found, this has implications for the first degree relatives of affected individuals who should also be offered genetic testing. Accordingly, the management of these patients should be undertaken using a multidisciplinary approach involving specialists in metabolic bone disease and clinical genetics.