FGF23-related hypophosphatemia in patients with low bone mineral density and fragility fractures: challenges in diagnosis and management

R. Indirli, G. Guabello, M. Longhi, S. Niada, K. Maruca, S. Mora, M. Maggioni, S. Corbetta

Research output: Contribution to journalArticle

Abstract

Purpose: Hypophosphatemia (HP) can be observed in patients evaluated for skeletal fragility. We investigated prevalence of HP among outpatients referred for low bone density or fragility fractures, HP-associated clinical and biochemical features and outcomes of recommended diagnostic algorithm in our cohort. Methods: Chronic HP (phosphate ≤ 2.7 mg/dL over 6 months or longer) was retrospectively investigated among 2319 patients. In renal wasting-related HP, intact FGF23 was assessed; non-suppressed FGF23 prompted the performance of 68Ga-DOTATOC PET/CT in the suspicion of tumor-induced steomalacia (TIO). Results: Renal wasting-related HP (median 2.2, range 1.6–2.6 mg/dL) was observed in 19 patients (0.82%). FGF23 levels were suppressed in two patients diagnosed with renal tubular disease, increased in one and within normal range in most patients. X-linked hypophosphatemic rickets was diagnosed in one woman. In the remaining 16 patients, highly prevalent fragility fractures (50%) and severely reduced bone mineral density were detected, though diagnostic criteria for osteomalacia were not fulfilled. 68Ga-PET was performed in nine patients and was positive in four. While intact FGF23 levels alone failed to differentiate PET’s outcomes (positive: FGF23 median 70.5 pg/mL; negative: 52 pg/mL, P = 0.462), the coexistence of multiple biochemical and radiologic alterations performed better in prediction of PET’s positivity. Conclusion: Mild, apparently unexplained HP is observed in 0.82% of patients with low bone density or fragility fractures. In asymptomatic patients with isolated mild hypophosphatemia, the probability of finding an underlying tumor disease is very low, and utility of extensive and expensive diagnostic workup should be carefully considered in this setting.

Original languageEnglish
JournalJournal of Endocrinological Investigation
DOIs
Publication statusAccepted/In press - Jan 1 2019

Keywords

  • Fibroblast growth factor 23
  • Hypophosphatemia
  • Low bone mineral density
  • Skeletal fragility
  • Tumor-induced osteomalacia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

@article{d72aa0a5de7549c5916cd06abcf3e8ec,
title = "FGF23-related hypophosphatemia in patients with low bone mineral density and fragility fractures: challenges in diagnosis and management",
abstract = "Purpose: Hypophosphatemia (HP) can be observed in patients evaluated for skeletal fragility. We investigated prevalence of HP among outpatients referred for low bone density or fragility fractures, HP-associated clinical and biochemical features and outcomes of recommended diagnostic algorithm in our cohort. Methods: Chronic HP (phosphate ≤ 2.7 mg/dL over 6 months or longer) was retrospectively investigated among 2319 patients. In renal wasting-related HP, intact FGF23 was assessed; non-suppressed FGF23 prompted the performance of 68Ga-DOTATOC PET/CT in the suspicion of tumor-induced steomalacia (TIO). Results: Renal wasting-related HP (median 2.2, range 1.6–2.6 mg/dL) was observed in 19 patients (0.82{\%}). FGF23 levels were suppressed in two patients diagnosed with renal tubular disease, increased in one and within normal range in most patients. X-linked hypophosphatemic rickets was diagnosed in one woman. In the remaining 16 patients, highly prevalent fragility fractures (50{\%}) and severely reduced bone mineral density were detected, though diagnostic criteria for osteomalacia were not fulfilled. 68Ga-PET was performed in nine patients and was positive in four. While intact FGF23 levels alone failed to differentiate PET’s outcomes (positive: FGF23 median 70.5 pg/mL; negative: 52 pg/mL, P = 0.462), the coexistence of multiple biochemical and radiologic alterations performed better in prediction of PET’s positivity. Conclusion: Mild, apparently unexplained HP is observed in 0.82{\%} of patients with low bone density or fragility fractures. In asymptomatic patients with isolated mild hypophosphatemia, the probability of finding an underlying tumor disease is very low, and utility of extensive and expensive diagnostic workup should be carefully considered in this setting.",
keywords = "Fibroblast growth factor 23, Hypophosphatemia, Low bone mineral density, Skeletal fragility, Tumor-induced osteomalacia",
author = "R. Indirli and G. Guabello and M. Longhi and S. Niada and K. Maruca and S. Mora and M. Maggioni and S. Corbetta",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s40618-019-01165-9",
language = "English",
journal = "Journal of Endocrinological Investigation",
issn = "0391-4097",
publisher = "Springer International Publishing",

}

TY - JOUR

T1 - FGF23-related hypophosphatemia in patients with low bone mineral density and fragility fractures

T2 - challenges in diagnosis and management

AU - Indirli, R.

AU - Guabello, G.

AU - Longhi, M.

AU - Niada, S.

AU - Maruca, K.

AU - Mora, S.

AU - Maggioni, M.

AU - Corbetta, S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: Hypophosphatemia (HP) can be observed in patients evaluated for skeletal fragility. We investigated prevalence of HP among outpatients referred for low bone density or fragility fractures, HP-associated clinical and biochemical features and outcomes of recommended diagnostic algorithm in our cohort. Methods: Chronic HP (phosphate ≤ 2.7 mg/dL over 6 months or longer) was retrospectively investigated among 2319 patients. In renal wasting-related HP, intact FGF23 was assessed; non-suppressed FGF23 prompted the performance of 68Ga-DOTATOC PET/CT in the suspicion of tumor-induced steomalacia (TIO). Results: Renal wasting-related HP (median 2.2, range 1.6–2.6 mg/dL) was observed in 19 patients (0.82%). FGF23 levels were suppressed in two patients diagnosed with renal tubular disease, increased in one and within normal range in most patients. X-linked hypophosphatemic rickets was diagnosed in one woman. In the remaining 16 patients, highly prevalent fragility fractures (50%) and severely reduced bone mineral density were detected, though diagnostic criteria for osteomalacia were not fulfilled. 68Ga-PET was performed in nine patients and was positive in four. While intact FGF23 levels alone failed to differentiate PET’s outcomes (positive: FGF23 median 70.5 pg/mL; negative: 52 pg/mL, P = 0.462), the coexistence of multiple biochemical and radiologic alterations performed better in prediction of PET’s positivity. Conclusion: Mild, apparently unexplained HP is observed in 0.82% of patients with low bone density or fragility fractures. In asymptomatic patients with isolated mild hypophosphatemia, the probability of finding an underlying tumor disease is very low, and utility of extensive and expensive diagnostic workup should be carefully considered in this setting.

AB - Purpose: Hypophosphatemia (HP) can be observed in patients evaluated for skeletal fragility. We investigated prevalence of HP among outpatients referred for low bone density or fragility fractures, HP-associated clinical and biochemical features and outcomes of recommended diagnostic algorithm in our cohort. Methods: Chronic HP (phosphate ≤ 2.7 mg/dL over 6 months or longer) was retrospectively investigated among 2319 patients. In renal wasting-related HP, intact FGF23 was assessed; non-suppressed FGF23 prompted the performance of 68Ga-DOTATOC PET/CT in the suspicion of tumor-induced steomalacia (TIO). Results: Renal wasting-related HP (median 2.2, range 1.6–2.6 mg/dL) was observed in 19 patients (0.82%). FGF23 levels were suppressed in two patients diagnosed with renal tubular disease, increased in one and within normal range in most patients. X-linked hypophosphatemic rickets was diagnosed in one woman. In the remaining 16 patients, highly prevalent fragility fractures (50%) and severely reduced bone mineral density were detected, though diagnostic criteria for osteomalacia were not fulfilled. 68Ga-PET was performed in nine patients and was positive in four. While intact FGF23 levels alone failed to differentiate PET’s outcomes (positive: FGF23 median 70.5 pg/mL; negative: 52 pg/mL, P = 0.462), the coexistence of multiple biochemical and radiologic alterations performed better in prediction of PET’s positivity. Conclusion: Mild, apparently unexplained HP is observed in 0.82% of patients with low bone density or fragility fractures. In asymptomatic patients with isolated mild hypophosphatemia, the probability of finding an underlying tumor disease is very low, and utility of extensive and expensive diagnostic workup should be carefully considered in this setting.

KW - Fibroblast growth factor 23

KW - Hypophosphatemia

KW - Low bone mineral density

KW - Skeletal fragility

KW - Tumor-induced osteomalacia

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U2 - 10.1007/s40618-019-01165-9

DO - 10.1007/s40618-019-01165-9

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JO - Journal of Endocrinological Investigation

JF - Journal of Endocrinological Investigation

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