I47. Paget’s Disease and Other Metabolic Bone Disorders

Abstract

Metabolic bone disorders comprise relatively common conditions such as Paget's disease of bone (PDB), osteomalacia secondary to nutritional deficiency of vitamin D, chronic kidney disease metabolic bone disorder (CKD-MBD) and primary hyperparathyroidism. Rarer conditions include fibrous dysplasia, and familial disorders exemplified by sex linked hypophosphataemic rickets. As well as referrals to rheumatology clinics, it is not uncommon for patients with these disorders to be identified following referral for DXA scans, for example following a low trauma fracture. This talk will focus on two of these conditions, namely PDB and CKD-MBD. PDB is usually diagnosed from a combination of an isolated elevation in alkaline phosphatase (ALP) and typical radiological features. The main indication for treatment, in the form of bisphosphonates, is bone pain; suppression of metabolic activity through decreased osteoclast activity is generally very effective. The newer amino-bisphosphonates such as risedronate, alendronate and zoledronate are treatments of choice. Trials comparing the efficacy of these agents in terms of symptomatic improvement have shown similar effects, but zoledronate is superior in terms of the extent and duration of suppression of disease markers such as ALP. Whereas bone pain due to PDB is an indication for bisphosphonate treatment, patients may require further radiological assessment to confirm that the pain is caused by active disease as opposed to a complication such as OA. In cases of uncertainty, a trial of bisphosphonates may be warranted. Whereas bisphosphonates have also been advocated in PDB to prevent the development of subsequent complications, there is little objective evidence to suggest these are helpful in treating clinical endpoints beyond pain. CKD-MBD may become apparent in patients with CKD stage 4-5 after finding raised levels of phosphate and PTH and/or reduced levels of calcium. One challenge is to distinguish this condition from osteoporosis, since both can present with low trauma fractures and reduced BMD on DXA, but only the former should be treated with anti-resorptive agents such as bisphosphonates. There are two main treatment goals in CKD-MBD namely to achieve neutral phosphate balance, and to prevent secondary and ultimately tertiary hyperparathyroidism. Neutral phosphate balance is generally achieved through a combination of dietary restriction and use of phosphate binders. In preventing secondary hyperparathyroidism, the main driver is impaired conversion of 25(OH)D to 1,25(OH)2D, reflecting decreased activity of renal 1-ahydroxylase activity, partly due to elevated FGF23. This has led to the use of activated forms of vitamin D in CKD-MBD, such as alfacalcidol and calcitriol, doses of which need to be carefully titrated against calcium levels. However, due to the morbidity caused by vascular calcification in CKD, cinacalcet may represent a safer strategy since this achieves reductions in PTH secretion by binding the calcium sensing receptor directly, without increasing calcium levels.