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Frequency, diagnosis, pathogenesis and management of osteoporosis in alkaptonuria: data analysis from the UK National Alkaptonuria Centre

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Abstract

Summary

Osteoporosis and fractures are common features of alkaptonuria.

Introduction

A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and fractures in AKU.

Methods

Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. CT BMD Z-scores were generated.

Results

Between June 2007 and March 2020, 87 AKU patients attended the NAC. At baseline, there were 48 fractures in 39 patients. Prevalence of osteoporosis was 3.1 at FN, 10.8 at TH and 24.7% at LS respectively. Prevalence of fragility fractures was greatly increased at 44.8%. The group with fractures showed increased ochronosis scores (p < 0.05). CT LS showed an inverse relationship with fractures (R = − 0.28; p < 0.05). CT LS was significantly lower in the fracture group (p < 0.002). Following nitisinone only, CT FN and CT TH decreased significantly (p < 0.05 and 0.01 respectively). Following nitisinone plus antiresorptive therapy, CT FN, CT TH and CT LS all increased significantly (p < 0.05, 0.05 and 0.001 respectively). However, patients on nitisinone plus antiresorptive had more fractures than nitisinone and no-treatment groups (p < 0.05).

Conclusions

Osteopenia and fragility fractures are common in AKU.. Anti-resorptive therapy increased BMD in AKU without decreasing fragility fractures. Bone densitometry measurements by DXA are less reliable than quantitative CT at the LS in AKU.

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Data availability

Lakshminarayan Ranganath, Milad Khedr, Sobhan Vinjamuri and James Gallagher agree to honour any reasonable request by other researchers for materials, methods or data necessary to verify the conclusion of the article.

Abbreviations

AKU:

Alkaptonuria

HGA:

Homogentisic acid

sHGA:

Serum homogentisic acid

uHGA24 :

24-h urine homogentisic acid

25OHD:

25-Hydroxyvitamin D

CTX:

Carboxy-terminal cross-linked telopeptide of type 1 collagen

PINP:

Procollagen type 1 amino-peptide propeptide

NOF:

CT BMD neck of femur

HIP:

CT BMD total hip

L2–L4:

CT BMD L2–L4

FT4:

Free thyroxine

NAC:

National Alkaptonuria Centre

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Acknowledgements

We wish to thank the staff at the NAC in particular Miss Hollie Washington and Miss Leanne A Evans for their important support to bring patients to the NAC. We thank the AKU Society, UK, who have also supported patients and the NAC making this work possible.

Funding

This work was supported by funding granted in April 2012 by the NHS England Highly Specialized Services in establishing the UK National Alkaptonuria Centre in the Royal Liverpool University Hospital.

Author information

Authors and Affiliations

  1. Departments of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK

    L. R. Ranganath & M. Khedr

  2. IACD, University of Liverpool, William Henry Duncan Building, West Derby Street, Liverpool, L7 8TX, UK

    L. R. Ranganath & J. A. Gallagher

  3. Nuclear Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK

    S. Vinjamuri

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  1. L. R. Ranganath
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Corresponding author

Correspondence to L. R. Ranganath.

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Ethics approval

The Natural History Study was approved by NW REC: 07/Q1002/111, and this yielded data collected between 2007 and 2011; The rest of the data collected from the NAC was approved by the Institutional Audit Committee (Audit No: ACO3836), for annual audit.

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The funding source was not involved in the study design, collection, analysis and interpretation of data, the writing of the manuscript, or in the decision to submit the manuscript for publication. The authors confirm independence from the funders; the content of the article has not been influenced by the funders.

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Ranganath, L.R., Khedr, M., Vinjamuri, S. et al. Frequency, diagnosis, pathogenesis and management of osteoporosis in alkaptonuria: data analysis from the UK National Alkaptonuria Centre. Osteoporos Int 32, 927–938 (2021). https://doi.org/10.1007/s00198-020-05671-y

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