Osteomalacia epidemiology and demographics
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Osteomalacia is the softening of the bones caused by deactivated bone mineralization primarily due to inadequate levels of available phosphate and calcium, or because of resorption of calcium. Osteomalacia in children is known as rickets, and because of this, use of the term "osteomalacia" is often restricted to the milder, adult form of the disease. Signs and symptoms can include diffuse body pains, muscle weakness, and fragility of the bones.
Epidemiology and Demographics
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor(s)-in-Chief: Ibrahim Elkhayat, M.B.B.Ch.[3]
The true prevalence of osteomalacia is uncertain because clinically apparent disease is often nonspecific or underrecognized, and there is no universally validated non-invasive case definition. Most osteomalacia is nutritional (calcipenic), whereas phosphopenic and hereditary forms are comparatively rare.[1][2]
Overall burden and the "hidden iceberg"
- In an autopsy study of 675 adults from northern Europe, histomorphometric osteomalacia, defined by osteoid volume/bone volume >2%, was present in approximately 26% of iliac-crest biopsies. Mineralization defects occurred in both sexes and across age groups.[3]
- Among adults older than 45 years presenting with low-energy hip fractures, histologic osteomalacia was identified in 26.7% (19/72) of patients. Biochemical criteria identified substantially higher proportions, approximately 41.7–75%, depending on the criteria used.[4]
- In contrast to histologic and biochemical estimates, clinically confirmed osteomalacia was identified in only 29 of 25,379 adults undergoing vitamin D testing in a North-East Scotland cohort, illustrating the substantial gap between clinically overt disease and broader histologic or biochemical definitions.[5]
- Vitamin D deficiency is substantially more common than osteomalacia and should not be used as a direct surrogate for osteomalacia prevalence.[1]
At-risk populations
Population groups bearing a disproportionate burden of nutritional osteomalacia include:
- People with darker skin pigmentation, particularly immigrant and ethnic-minority populations living at higher latitudes, in whom vitamin D deficiency occurs at substantially higher rates than in background populations.[2]
- People with limited effective ultraviolet exposure, including those living at high latitudes, people wearing extensive skin-covering clothing, institutionalized populations, and individuals with substantial sun avoidance.[2]
- Older and institutionalized adults, particularly those presenting with low-energy fractures, in whom histologic osteomalacia is relatively common.[4]
- Pregnant and lactating women, particularly dark-skinned immigrant populations living at high latitude. In a Swedish cohort of 123 pregnant or breastfeeding women, biochemical osteomalacia was identified in 20 participants, 19 of whom were Somali.[6]
- Patients after malabsorptive bariatric surgery, in whom vitamin D deficiency is common; overt osteomalacia is an uncommon but recognized late complication.[7]
Geographic and ethnic patterns
- In higher-latitude regions, seasonal reduction in ultraviolet-B exposure contributes to vitamin D deficiency, with a disproportionate burden among dark-skinned residents and immigrants.[2]
- In sunny, lower-latitude regions, including parts of the Indian subcontinent, Middle East, and Africa, nutritional osteomalacia may be driven by dietary calcium deficiency as well as vitamin D deficiency. Sun exposure does not eliminate risk, particularly where sun avoidance, concealing clothing, or dietary factors limit effective vitamin D or calcium availability.[2]
- Reported severe vitamin D deficiency, defined as 25-OHD <30 nmol/L, is approximately 5.9% in the United States, 7.4% in Canada, and 13% in Europe, but exceeds 20% in several countries and regions of South Asia and the Middle East. These are vitamin D deficiency estimates, not osteomalacia prevalence.[8]
- Population-level vitamin D deficiency estimates vary substantially by geography and study population and should not be interpreted as estimates of osteomalacia prevalence.[8]
Sex and age distribution
Histologic nutritional osteomalacia is not confined to women or older adults. In the large autopsy series, mineralization defects occurred in both sexes and across age groups, although specific populations such as older adults, institutionalized individuals, and pregnant or lactating women may carry a greater burden of nutritional disease.[3]
Phosphopenic and hereditary forms
Phosphopenic and hereditary osteomalacia are uncommon compared with nutritional disease.
- X-linked hypophosphatemia (XLH) is the most common form of hereditary hypophosphatemia, accounting for approximately 90% of hypophosphatemic rickets. Reported incidence is approximately 3.9 per 100,000 live births and prevalence approximately 1.7–4.8 per 100,000.[9][10]
- Tumor-induced osteomalacia (TIO) is a rare acquired FGF23-mediated disorder that usually presents during adulthood, with a mean age at onset of approximately 40–45 years. Sex distribution is debated: several reviews describe approximately equal involvement of men and women, whereas the largest individual-patient-data systematic review, comprising 1,725 cases, found TIO to be more frequent, and more severe, in adult men. There is no established ethnic predilection, and population-level incidence data remain limited.[11][12]
Underdiagnosis and epidemiologic uncertainty
The epidemiologic burden of osteomalacia is difficult to quantify because reported prevalence varies according to whether histologic, biochemical, or clinical definitions are used. The discrepancy is particularly evident in low-energy hip-fracture cohorts, in which biochemical criteria identify substantially more patients than histologic criteria.[1][4]
Underdiagnosis is particularly pronounced for TIO. A systematic clinical review of 895 cases reported diagnostic delays exceeding 2 years in more than 80% of patients, highlighting the substantial burden of delayed recognition.[13]
A low 25-hydroxyvitamin D concentration is not synonymous with osteomalacia. Conversely, osteomalacia can occur in populations in which vitamin D deficiency is not the sole nutritional determinant, particularly where dietary calcium deficiency is prevalent.[2]
References
- ↑ 1.0 1.1 1.2 Uday S; Högler W (2019). "Spot the Silent Sufferers: A Call for Clinical Diagnostic Criteria for Solar and Nutritional Osteomalacia". The Journal of Steroid Biochemistry and Molecular Biology. 188: 141–146. doi:10.1016/j.jsbmb.2019.01.004.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Uday S; Högler W (2017). "Nutritional Rickets and Osteomalacia in the Twenty-first Century: Revised Concepts, Public Health, and Prevention Strategies". Current Osteoporosis Reports. 15 (4): 293–302. doi:10.1007/s11914-017-0383-y.
- ↑ 3.0 3.1 Priemel M; von Domarus C; Klatte TO (2010). "Bone Mineralization Defects and Vitamin D Deficiency: Histomorphometric Analysis of Iliac Crest Bone Biopsies and Circulating 25-Hydroxyvitamin D in 675 Patients". Journal of Bone and Mineral Research. 25 (2): 305–312. doi:10.1359/jbmr.090728.
- ↑ 4.0 4.1 4.2 Mirghaderi P; Mortezaei A; Parry JA (2023). "Osteomalacia Prevalence, Biochemical Profile, and Histology in Patients With Low-Energy Hip Fractures Over the Age of 45". Calcified Tissue International. 113 (3): 257–265. doi:10.1007/s00223-023-01103-1.
- ↑ Macleod AD; Bolland MJ; Balfour A (2025). "Biochemical osteomalacia in adults undergoing vitamin D testing in the North-East of Scotland". Annals of Clinical Biochemistry. 62 (4): 303–311. doi:10.1177/00045632251315671.
- ↑ Paul K; Torstensson T; Per K (2025). "Biochemical Osteomalacia Reaffirmed by Signs and Symptoms and Perinatal Outcome. A Prospective Cohort Study of Women in Sweden". Bone: 117679. doi:10.1016/j.bone.2025.117679.
- ↑ Stein J; Stier C; Raab H; Weiner R (2014). "Review article: the nutritional and pharmacological consequences of obesity surgery". Alimentary Pharmacology & Therapeutics. 40 (6): 582–609. doi:10.1111/apt.12872.
- ↑ 8.0 8.1 Amrein K; Scherkl M; Hoffmann M (2020). "Vitamin D deficiency 2.0: an update on the current status worldwide". European Journal of Clinical Nutrition. 74 (11): 1498–1513. doi:10.1038/s41430-020-0558-y.
- ↑ Haffner D; Emma F; Seefried L (2025). "Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia". Nature Reviews Nephrology. 21 (5): 330–354. doi:10.1038/s41581-024-00926-x.
- ↑ Kamenický P; Briot K; Munns CF; Linglart A (2024). "X-Linked Hypophosphataemia". Lancet. 404 (10455): 887–901. doi:10.1016/S0140-6736(24)01305-9.
- ↑ Rendina D; Abate V; Cacace G (2022). "Tumor-Induced Osteomalacia: A Systematic Review and Individual Patient's Data Analysis". The Journal of Clinical Endocrinology and Metabolism. 107 (8): e3428–e3436. doi:10.1210/clinem/dgac253.
- ↑ Minisola S; Peacock M; Fukumoto S (2017). "Tumour-induced osteomalacia". Nature Reviews Disease Primers. 3: 17044. doi:10.1038/nrdp.2017.44.
- ↑ Bosman A; Palermo A; Vanderhulst J (2022). "Tumor-Induced Osteomalacia: A Systematic Clinical Review of 895 Cases". Calcified Tissue International. 111 (4): 367–379. doi:10.1007/s00223-022-01005-8.