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BMC Musculoskeletal Disorders

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Open Access 01-12-2016 | Research article

Hypophosphatasia and the risk of atypical femur fractures: a case–control study

Authors: Timothy Bhattacharyya, Smita Jha, Hongying Wang, Daniel L. Kastner, Elaine F. Remmers

Published in: BMC Musculoskeletal Disorders | Issue 1/2016

Abstract

Background

Case reports have linked adult hypophosphatasia as a possible cause of atypical femur fractures (AFF) associated with bisphosphonate use. Adult hypophosphatasia is an asymptomatic genetic condition which results in low alkaline phosphatase and elevated pyridoxal phosphate. We conducted a case–control study to assess the role of hypophosphatasia and atypical femur fracture.

Methods

We recruited 13 control patients who took long term bisphosphonates without complication and 10 patients who sustained atypical femur fractures (mean bisphosphonate use, 9 years both cohorts). Patients underwent clinical exam and measurement of alkaline phosphatase and pyridoxal phosphate (PLP) levels. In addition, DNA was extracted and the ALPL gene was sequenced in both cohorts.

Results

Low alkaline phosphatase levels (<55 U/L) were seen in 5/10 AFF patients and 5/13 control patients. Two control patients demonstrated low alkaline phosphatase levels and elevated PLP. The alkaline phosphatase (ALPL) gene exons and intron splice sites were sequenced in the atypical femur fracture and control cohorts and no coding mutations were identified in any subjects. Atypical femur fracture patients demonstrated more varus hip alignment (p < 0.048) with no significant difference in mechanical axis.

Conclusions

We found no evidence of hypophosphatasia as a risk factor for atypical femur fractures. Laboratory findings of mildly low alkaline phosphatase activity were equally common in atypical and control cohorts and may be due to long term bisphosphonate use.

Trial registration

Clinicaltrials.gov number NCT01360099. Prospectively registered May 20, 2011. First patient enrolled June 14, 2011.

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Title: Hypophosphatasia and the risk of atypical femur fractures: a case–control study
Authors: Timothy Bhattacharyya
Smita Jha
Hongying Wang
Daniel L. Kastner
Elaine F. Remmers
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Musculoskeletal Disorders / Issue 1/2016
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/s12891-016-1191-8

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Hypophosphatasia and the risk of atypical femur fractures: a case–control study

Abstract

Background

Methods

Results

Conclusions

Trial registration

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

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