Elevated Bone Remodeling Markers of CTX and P1NP in Addition to Sclerostin in Patients with X-linked Hypophosphatemia: A Cross-Sectional Controlled Study

  • Stinus HansenEmail author
  • Vikram V. Shanbhogue
  • Niklas Rye Jørgensen
  • Signe Sparre Beck-Nielsen
Original Research


Aspects of bone remodeling have only been scarcely studied in X-linked hypophosphatemia (XLH). In this cross-sectional controlled study, we assessed biochemical indices of bone remodeling and sclerostin in 27 adult patients (median age 47 [range 24–79] years, 19 women, 8 men) with XLH matched with 81 healthy control subjects (1:3) with respect to age-, sex-, and menopausal status. Markers of bone resorption (carboxyterminal cross-linked telopeptide of type 1 collagen, CTX) and formation (N-terminal propeptide of type 1 procollagen, P1NP) were higher in XLH patients compared to controls (median [IQR] 810 [500–1340] vs 485 [265–715] ng/l and 90 [57–136] vs 49 [39–65] ug/l, respectively, both p < 0.001) as well as sclerostin (0.81 [0.60–1.18] vs 0.54 [0.45–0.69] ng/ml, p < 0.001). Similar differences were found when comparing currently treated (with phosphate and alfacalcidol) (n = 11) and untreated (n = 16) XLH patients with their respective controls. We found no significant associations with treatment status and indices of bone remodeling or sclerostin although sclerostin tended to be increased in untreated versus treated (p = 0.06). In contrast to previous histomorphometric studies suggesting a low remodeling activity in XLH, these biochemical indices suggest high osteoblast and osteoclast activity. Further studies are needed to ascertain if the higher sclerostin level in XLH is related to osteocyte dysfunction or represents a secondary phenomenon.


X-linked hypophosphatemia Bone remodeling markers Sclerostin Phosphate Alfacalcidol 



This study was supported by a grant from The Research Foundation of the Region of Southern Denmark.

Author Contributions

Study design: SH, SBN, VS, NRJ. Study conduct: SBN, VS, SH. Data collection: SBN, VS, SH. Data interpretation: All authors. Drafting manuscript: SH. Revising manuscript: All authors. Approving final version of manuscript: All authors. SH takes responsibility for integrity of the data analysis. SBN is the overall guarantor of the work presented.

Compliance with Ethical Standards

Conflict of interest

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

Human and Animal Rights and Informed Consent

Informed consent was obtained from all individual participants included in the study and the Regional Scientific Ethical Committee for Southern Denmark approved the study (reference numbers S-20120155 and S-20090069).

Supplementary material

223_2019_526_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of EndocrinologyHospital South West JutlandEsbjergDenmark
  2. 2.Department of EndocrinologyOdense University HospitalOdenseDenmark
  3. 3.Department of Clinical BiochemistryRigshospitaletGlostrupDenmark
  4. 4.OPEN, Odense Patient Data Explorative Network, Odense University Hospital/Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
  5. 5.Department of PediatricsKolding Hospital at Lillebaelt HospitalKoldingDenmark
  6. 6.Department of Regional Health ResearchUniversity of Southern DenmarkOdenseDenmark

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