Phys · endocrine
Metabolic Bone Disease and Vitamin D Disorders
Also known as osteoporosis · vitamin D deficiency · osteomalacia · Paget disease · FRAX · denosumab rebound · drug holiday · atypical femoral fracture
Consultant-physician depth guide to osteoporosis (DEXA, FRAX, bisphosphonates, denosumab sequencing, anabolics), vitamin D deficiency and osteomalacia, Paget disease, and primary hyperparathyroidism bone disease — for FRACP DWE/DCE preparation.
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Target exams
Red flags
- Fragility fracture with T-score in osteoporotic range — treat the absolute risk, not the number alone; compute FRAX
- Denosumab stopped without bisphosphonate sequencing — rebound multiple vertebral fractures
- Bone pain with high ALP and normal GGT — Paget disease until proven otherwise; single zoledronic acid infusion
- Proximal myopathy with low vitamin D and high PTH — osteomalacia; replace substrate, not antiresorptive
Meet the patient
Meet a 72-year-old woman referred six weeks after a low-impact wrist fracture — she tripped on a curb and put out her hand. DXA shows a femoral-neck T-score of −2.8, she had a wrist fracture five years ago, her FRAX ten-year hip-fracture probability is 5 per cent, and she takes a proton-pump inhibitor for reflux. The real decision is not which bisphosphonate, but whether an oral agent is right for her at all.[1][12]
Two questions settle every metabolic bone case before any prescription: what is the mechanism (high-turnover osteoporosis, low-turnover adynamic bone, defective mineralisation, localised Paget disease, or parathyroid-driven resorption), and what is the absolute fracture risk over ten years by FRAX? Answer those two and the drug ladder writes itself.[5][12]
References13ShowHide
- [1]Black DM, Delmas PD, Eastell R, Reid IR, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis N Engl J Med, 2007.PMID 17476007
- [2]Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis N Engl J Med, 2009.PMID 19671655
- [3]Bone HG, Wagman RB, Brandi ML, Brown JP, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension Lancet Diabetes Endocrinol, 2017.PMID 28546097
- [4]Cummings SR, Ferrari S, Eastell R, Gilchrist N, et al. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension J Bone Miner Res, 2018.PMID 29105841
- [5]Schini M, Johansson H, Harvey NC, et al. An overview of the use of the fracture risk assessment tool (FRAX) in osteoporosis J Endocrinol Invest, 2024.PMID 37874461
- [6]Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, et al. Effect of Vitamin D on falls: a meta-analysis JAMA, 2004.PMID 15113819
- [7]Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials JAMA, 2005.PMID 15886381
- [8]Bolland MJ, Avenell A, Baron JA, Grey A, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis BMJ, 2010.PMID 20671013
- [9]Reid IR, Bolland MJ, Grey A Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis Lancet, 2014.PMID 24119980
- [10]Reid IR, Miller P, Lyles K, Fraser W, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease N Engl J Med, 2005.PMID 16135834
- [11]Bilezikian JP Primary Hyperparathyroidism J Clin Endocrinol Metab, 2018.PMID 30060226
- [12]Compston J, Cooper A, Cooper C, Gittoes N, et al. The 2024 UK clinical guideline for the prevention and treatment of osteoporosis Arch Osteoporos, 2025.PMID 40921943
- [13]Cianferotti L Osteomalacia Is Not a Single Disease Int J Mol Sci, 2022.PMID 36499221