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Impact of Conventional Medical Therapy on Bone Mineral Density and Bone Turnover in Adult Patients with X-Linked Hypophosphatemia: A 6-Year Prospective Cohort Study

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Abstract

X-linked hypophosphatemia (XLH) is a rare, inheritable disorder manifesting as rickets in children and osteomalacia in adults. While conventional medical treatment with oral phosphate and alfacalcidol is recommended in childhood, it is undecided whether adults should continue therapy. The aim of this 6-year prospective study was to determine the impact of conventional medical treatment on areal bone mineral density (aBMD), bone turnover markers (BTMs) and measures of calcium homeostasis in 27 adult patients with XLH, 11 of whom received medical treatment. Lumbar spine and total hip aBMD, as assessed by DXA, and biochemical measures of calcium, phosphate, PTH, 1,25 dihydroxyvitamin D2+3 (1,25(OH)2D), fibroblast growth factor 23 (FGF23), P1NP and CTX were measured at baseline and at follow-up. The renal tubular reabsorption of PO4 (TmPO4/GFR) was calculated at both time points. Multilevel mixed-effects linear regression models were used for analyses. During the study period, spine and hip aBMD did not change significantly between treated and non-treated XLH patients. There was a trend towards a decrease in calcium, phosphate and TmPO4/GFR in the treatment group (p = 0.057, p = 0.080 and p = 0.063, respectively), whereas PTH, FGF23, 1,25(OH)2D and P1NP did not change significantly in either groups. However, CTX increased significantly in the treated compared to non-treated group (p = 0.044). Continuing conventional medical therapy in adulthood, although associated with increased bone resorption, does not promote or prevent loss of bone mass as evidenced from the stable aBMD of the hip and spine in XLH patients.

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Acknowledgements

The authors thank Lotte Hørlyck and Elizabeth Hanmann for their help in coordinating the study and all the technical staff at the Osteoporosis Clinic, Odense University Hospital in obtaining consent from the participants and performing the bone scans. This study was supported by a grant from The Research Foundation of the Region of Southern Denmark.

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Authors and Affiliations

  1. Department of Endocrinology, Odense University Hospital, Odense, Denmark

    Vikram Vinod Shanbhogue & Stinus Hansen

  2. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

    Vikram Vinod Shanbhogue & Stinus Hansen

  3. Department of Clinical Biochemistry, Rigshospitalet, Glostrup, Denmark

    Niklas Rye Jørgensen

  4. OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

    Niklas Rye Jørgensen

  5. Department of Pediatrics, Kolding Hospital at Lillebaelt Hospital, Sygehusvej 24, DK-6000, Kolding, Denmark

    Signe Sparre Beck-Nielsen

  6. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

    Signe Sparre Beck-Nielsen

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  1. Vikram Vinod Shanbhogue
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Contributions

Study design: VS, SBN. Study conduct: VS, SBN. Data collection: SBN Data analysis: VS, SH, SBN. Data interpretation: VS, SH, NRJ, SBN. Drafting 17 manuscript: VS. Revising manuscript content: VS, SH, SBN. Approving final version of manuscript: VS, SH, NRJ, SBN. VS, SH and SBN take responsibility for the integrity of the data analysis.

Corresponding author

Correspondence to Signe Sparre Beck-Nielsen.

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Conflicts of interest

Signe Sparre Beck-Nielsen received a payment from Pharmacosmos for participation in an expert meeting and a payment from Kyowa Kirin for an invited speech. She also provides consultancy to Strakan International. Vikram V Shanbhogue, Stinus Hansen and Niklas Rye Jørgensen declare that they have no conflict of interest.

Ethical Approval

All procedures performed were in accordance with the ethical standards of the Declaration of Helsinki and approved by the Regional Scientific Ethical Committee of Southern Denmark.

Human and Animal Rights and Informed Consent

All participants provided verbal and written informed consent, and the baseline and the follow-up study were performed according to the guidelines of the Declaration of Helsinki and approved by the Regional Scientific Ethical Committee of Southern Denmark (Ref. IDs M-2678-05 and S-20120155, respectively).

Additional information

Vikram Vinod Shanbhogue and Stinus Hansen share first authorship.

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Shanbhogue, V.V., Hansen, S., Jørgensen, N.R. et al. Impact of Conventional Medical Therapy on Bone Mineral Density and Bone Turnover in Adult Patients with X-Linked Hypophosphatemia: A 6-Year Prospective Cohort Study. Calcif Tissue Int 102, 321–328 (2018). https://doi.org/10.1007/s00223-017-0363-3

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  • DOI: https://doi.org/10.1007/s00223-017-0363-3

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