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Bone involvement and mineral metabolism in Williams’ syndrome

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Abstract

Context

The previous studies suggested a possible increased risk of hypercalcaemia and reduced bone mineral density (BMD) in Williams’ syndrome (WS). However, an extensive study regarding bone metabolism has never been performed.

Objective

To investigate bone health in young adults with WS.

Design

Cross-sectional study.

Settings

Endocrinology and Metabolic Diseases and Medical Genetic Units.

Patients

29 WS young adults and 29 age- and sex-matched controls.

Main outcome measures

In all subjects, calcium, phosphorus, bone alkaline phosphatase (bALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHVitD), osteocalcin (OC), carboxyterminal cross-linking telopeptide of type I collagen (CTX), 24-h urinary calcium and phosphorus, femoral-neck (FN) and lumbar-spine (LS) BMD and vertebral fractures (VFx) were assessed. In 19 patients, serum fibroblast growth factor-23 (FGF23) levels were measured.

Results

WS patients showed lower phosphorus (3.1 ± 0.7 vs 3.8 ± 0.5 mg/dL, p = 0.0001) and TmP/GFR (0.81 ± 0.32 vs 1.06 ± 0.25 mmol/L, p = 0.001), and an increased prevalence (p = 0.005) of hypophosphoremia (34.5 vs 3.4%) and reduced TmP/GFR (37.9 vs 3.4%). Moreover, bALP (26.3 ± 8.5 vs 35.0 ± 8.0 U/L), PTH (24.5 ± 12.6 vs 33.7 ± 10.8 pg/mL), OC (19.4 ± 5.3 vs 24.5 ± 8.7 ng/mL), and FN-BMD (− 0.51 ± 0.32 vs 0.36 ± 0.32) were significantly lower (p < 0.05), while CTX significantly higher (401.2 ± 169.3 vs 322.3 ± 122.4 pg/mL, p < 0.05). Serum and urinary calcium and 25OHVitD levels, LS-BMD and VFx prevalence were comparable. No cases of hypercalcemia and suppressed FGF23 were documented. Patients with low vs normal phosphorus and low vs normal TmP/GFR showed comparable FGF23 levels. FGF23 did not correlate with phosphorus and TmP/GFR values.

Conclusions

Adult WS patients have reduced TmP/GFR, inappropriately normal FGF23 levels and an uncoupled bone turnover with low femoral BMD.

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Author information

Authors and Affiliations

  1. Department of Medical Sciences and Community Health, University of Milan, Milan, Italy

    S. Palmieri, E. Cairoli, A. M. Barbieri, A. Spada & I. Chiodini

  2. Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy

    S. Palmieri, V. Morelli, M. E. Lunati, A. M. Barbieri, E. Orsi & C. Eller-Vainicher

  3. Medical Genetic Unit, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy

    M. F. Bedeschi & F. Lalatta

  4. Unit of Endocrinology, “Casa Sollievo della Sofferenza”, Hospital, IRCCS, San Giovanni Rotondo, Foggia, Italy

    A. Scillitani

  5. Unit of Internal Medicine, “Casa Sollievo della Sofferenza”, Hospital, IRCCS, San Giovanni Rotondo, Foggia, Italy

    V. Carnevale

  6. Unit for Bone Metabolism Diseases and Diabetes and Lab of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, Milan, Italy

    I. Chiodini

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  1. S. Palmieri
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  2. M. F. Bedeschi
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  3. E. Cairoli
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  7. V. Carnevale
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  13. C. Eller-Vainicher
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Corresponding author

Correspondence to S. Palmieri.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Palmieri, S., Bedeschi, M.F., Cairoli, E. et al. Bone involvement and mineral metabolism in Williams’ syndrome. J Endocrinol Invest 42, 337–344 (2019). https://doi.org/10.1007/s40618-018-0924-y

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