Subtrochanteric and diaphyseal femoral fractures in hypophosphatasia—not atypical at all

Original Article
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Abstract

Summary

Risk for subtrochanteric and diaphyseal femoral fractures is considered increased in patients with hypophosphatasia (HPP). Evaluating a large cohort of HPP patients, we could for the first time quantify the prevalcence and identify both morphometric features as well as predisposing factors for this complication of severe HPP.

Introduction

Subtrochanteric and diaphyseal femoral fractures have been associated with both, long-term antiresorptive treatment and metabolic bone disorders, specifically Hypophosphatasia (HPP). Building on a cross-sectional evaluation of real-world data, this study reports risk factors, prevalence, treatment outcome and morphometric particularities for such fractures in HPP as compared to Atypical Femoral Fractures (AFF) in long-term antiresorptive treatment.

Methods

For 15 out of 150 HPP patients identified with having experienced at least one such fracture, medical records were reviewed in detail, extracting medical history, genotype, lab assessments, bone mineral density (DXA), radiographic data on femoral geometry and clinical aspects of fracture etiology and healing.

Results

Bilateral fractures were documented in 10 of these 15 patients, yielding a total of 25 fractures for evaluation. Disease-inherent risk factors included autosomal-recessive, childhood onset HPP, apparently low alkaline phosphatase (ALP) ≤ 20 U/l and substantially elevated pyridoxal 5′-phosphate (PLP) > 3 times upper limit of normal as well as high lumbar spine BMD. Fracture morphology met definition criteria for AFF in 88% of cases. Femoral geometry revealed additional risk factors previously described for AFF, including decreased femoral neck-shaft angle and increased femoral offset. Extrinsic risk factors include Hypovitaminosis D (80%) and pre-treatment with bisphosphonates (46,7%) and Proton-Pump Inhibitors (40%).

Conclusions

Increased risk for subtrochanteric and diaphyseal femoral fractures in HPP appears to result from both compromised bone metabolism as well as disease-associated bone deformities. In severe HPP, generous screening for such fractures seems advisable. Bisphosphonates and Hypovitaminosis D should be avoided. Healing is compromised and requires mindful consideration of both pharmacological and surgical options.

Keywords

Atypical femoral fractures Bisphosphonates Femoral geometry Hypophosphatasia 

Notes

Acknowledgements

We thank Jasmin Baumann, Silke Achtziger, Ursula Hellwich, and Nicole Luksche for their highly valued assistance with data collection and archiving.

Compliance with ethical standards

Conflicts of interest

FG reports personal fees from Lilly during the course of the study.

LS reports grants and personal fees from Novartis and Alexion and personal fees from Lilly and Amgen during the course of the study.

Statement

This study is a retrospective evaluation of clinical routine data. For this type of study, formal consent is not required.

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Clinical Trial Unit, Orthopedic DepartmentUniversity of WuerzburgWuerzburgGermany

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