Osteomalacia in Adults: A Practical Insight for Clinicians
Abstract
:1. Introduction
2. Rickets and Osteomalacia
3. Phosphate as a Key Element of Bone Mineralization
3.1. General Aspects of Phosphate Homeostasis
3.2. Hormonal Control of Inorganic Phosphate
3.3. Fibroblast Growth Factor 23 (FGF-23)
4. Clinical Diagnosis of Osteomalacia
5. Etiology of Osteomalacia
5.1. Nutritional Osteomalacia
- Asymptomatic calcium deprivation phase: only initial biochemical signs are observed, mainly calcidiol below 15 ng/mL, PTH above 50 pg/mL, and a moderately decreased urinary Ca/Cr ratio;
- Pre-OM phase: the previous biochemical signs are more pronounced, with secondary hyperparathyroidism already existing and total alkaline phosphatase beginning to rise. We can observe a decreased serum calcium or phosphate and if we had the option of performing a bone histomorphometry, hyperosteoidosis would already be observed in the static study and delayed mineralization time in the dynamic study of double labeling with tetracycline. In this phase, there are usually no signs on imaging tests, although OM is already beginning to manifest clinically: patients report, to a variable degree, musculoskeletal pain, recurrent falls, hypotonia and muscle weakness, fatigue, and bone fragility, while presenting fractures that are generally wrongly attributed to osteoporosis;
- OM phase: in this phase, signs are observed in the imaging tests, which are added to the previous clinical picture.
5.2. X-Linked Hypophosphatemia
5.3. Oncogenic Osteomalacia
5.4. Drug-Induced Osteomalacia
5.4.1. Methotrexate
5.4.2. Intravenous Iron Salts
5.4.3. Drug-Induced Tubulopathies/Fanconi Syndrome
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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1. Japanese Criteria [20] |
(a) Hypophosphatemia or hypocalcemia; (b) Elevated bone alkaline phosphatase; (c) Muscle weakness or bone pain; (d) BMD <80% in young adults; (e) Image: multiple uptake bone zones or Looser–Milkman fractures. |
Defined OM: a–e. Probable OM: a+b and 2 out of c–e. BMD: Bone mineral density. |
2. Uday–Hogler Criteria [21] |
(a) Elevated parathormone (PTH); (b) Elevated total alkaline phosphatase; (c) Calcium intake <300 mg/d or serum calcidiol <30 nmol/L; (d) Low urinary calcium. |
The above criteria, applied in the absence of kidney or liver disease, suggest the diagnosis of OM. The additional presence of symptoms and Looser zones helps in advanced phases. |
Name | Gen | Hereditary Transmission | Clinical Picture |
---|---|---|---|
XLH | PHEX | X-linked | Post rickety sequelae. Hypophosphatemia. Low calcitriol |
ADHR | FGF23 | AD | Similar to XLH |
ARHR1 | DMP1 | AR | Similar to XLH |
ARHR2 | ENPP1 | AR | Similar to XLH with arterial calcifications in childhood (GACI syndrome) |
ARHR3 | FAM20c | AR | Hypophosphatemia with osteosclerosis, facial dysmorphia, brain calcifications, and severe dental alterations |
OGD | FGFR1 | Hypophosphatemic rickets with craniosynostosis, facial dysmorphism, and dwarfism | |
McCune–Albright syndrome | Sporadic congenital disorders due to postzygotic mutations in genes that activate the signal or levels of FGF23 | Classic triad: precocious puberty, café au lait spots, and fibrous dysplasia. Associated rickets is rare and is due to FGF23 production by bone lesions. | |
TIO | Severe acquired hypophosphatemia secondary to ectopic production of FGF23. There may be hypocalcemia caused by a decrease in FGF23 dependent on the synthesis of calcitriol. | ||
HHRH | SLC34A3 | AR | Postrickets sequelae, hypophosphatemia, hypercalciuria, and lithiasis with nephrocalcinosis. |
HRHPT | α-KLOTHO | AD | Macrocephaly, dysplasia of the nasal bones, hypercalcemia, and hyperparathyroidism. |
Congenital and acquired tubulopathies | They can affect the elimination of phosphates in an isolated way or within Fanconi syndrome. |
Place | Latitude | July | December |
---|---|---|---|
Sapporo (Japan) | 43.06 N | 4.6–7.4 | 76.4–497.4 |
Asturias (Spain) | 44.46 N | 6 | 286 |
Tsukuba (Japan) | 32.02 N | 3.5–5.9 | 22.4–106.0 |
Cadiz (Spain) | 36.32 N | 4–5 | 64 |
Naha (Japan) | 26.12 N | 2.9–8.8 | 7.5–78.0 |
Tenerife (Spain) | 28.0 N | 6 | 43 |
Drug Class | Drug |
---|---|
Analgesics | Acetaminophen [85] |
Antiandrogens | Abiraterone acetate [86] |
Anticonvulsants | Phenytoin [87], topiramate [87] |
Antineoplasics | Elotuzumab [88] Lenalidomide [89], Cabozantinib [90], Ceritinib [91], Cobimetinib [92], Crizotinib [93], Dabrafenib [94], Imatinib [95], Nilotinib [96], Sorafenib [97], Regorafenib [98], Cis-platinum [99], Ifosfamide [100] |
mTOR inhibitors | Sirolimus [101], Everolimus [101], Temsirolimus [101] |
Calcineurin inhibitors | Cyclosporine [102], Tacrolimus [103] |
Antiresorptives | Zoledronate [104], Etidronate [105], Alendronate [105], Denosumab [106] |
Diuretics | Thiazides [107] |
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Arboleya, L.; Braña, I.; Pardo, E.; Loredo, M.; Queiro, R. Osteomalacia in Adults: A Practical Insight for Clinicians. J. Clin. Med. 2023, 12, 2714. https://doi.org/10.3390/jcm12072714
Arboleya L, Braña I, Pardo E, Loredo M, Queiro R. Osteomalacia in Adults: A Practical Insight for Clinicians. Journal of Clinical Medicine. 2023; 12(7):2714. https://doi.org/10.3390/jcm12072714
Chicago/Turabian StyleArboleya, Luis, Ignacio Braña, Estefanía Pardo, Marta Loredo, and Rubén Queiro. 2023. "Osteomalacia in Adults: A Practical Insight for Clinicians" Journal of Clinical Medicine 12, no. 7: 2714. https://doi.org/10.3390/jcm12072714