Outcome of Teriparatide Treatment on Fracture Healing Complications and Symptomatic Bone Marrow Edema in Four Adult Patients With Hypophosphatasia.

Tobias Schmidt,Nico Maximilian Jandl,Ralf Oheim,Tim Rolvien,Carolin Linke,Michael Amling,Florian Barvencik

doi:10.1002/jbm4.10215

Tobias Schmidt, Nico Maximilian Jandl + Show 5 more

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https://doi.org/10.1002/jbm4.10215

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Journal: JBMR plus	Publication Date: Aug 1, 2019
Citations: 14	License type: CC BY 4.0

Affiliation: University Medical Center Hamburg-Eppendorf

Abstract

ABSTRACTThe response to teriparatide has been described in very few cases of hypophosphatasia (HPP). In this cross‐sectional study, we report the prevalence of symptomatic bone marrow edema (BME) and fracture healing complications in a large cohort of childhood and adult HPP patients and discuss the results of teriparatide treatment in four cases. From 2016 to 2018, 51 patients with a diagnosis of HPP were seen at our institution. The diagnosis of HPP was established by low serum alkaline phosphatase (ALP), elevated serum pyridoxal‐5‐phosphate (PLP), at least one typical clinical symptom of HPP and supported by ALPL mutation analysis. In this study cohort, 28 (56%) and 14 (27%) patients had a history of fracture or a history of BME, respectively. Four patients, including middle‐aged to elderly women and men who all presented with persistent symptomatic BME or fracture healing complications, were treated with teriparatide. DXA was performed prior to treatment and laboratory values were measured on a regular basis during treatment. Treatment with teriparatide showed variable effects in terms of clinical and biochemical response. Although all four patients displayed a temporary increase in ALP activity, only two patients with a mild form of adult HPP and moderately increased PLP levels showed definite clinical and radiological improvement after teriparatide treatment. In conclusion, fracture healing complications and BME occur frequently in HPP patients. Teriparatide shows variable clinical and biochemical effects depending on the severity of the disease. PLP levels and the number of ALPL alleles might be good parameters to predict treatment outcomes. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research

Highlights

Hypophosphatasia (HPP) is a rare inherited disease caused by a loss of function mutation within the gene ALPL encoding the tissue nonspecific alkaline phosphatase (TNSALP).(1) Deficient alkaline phosphatase (ALP) activity leads to an accumulation of its substrates including pyridoxal‐5‐phosphate (PLP) and inorganic pyrophosphate (PPi)
We report the prevalence of fractures and bone marrow edema (BME) in a large cohort of children and adults with low ALP activity and report the outcome of 4 patients with adult HPP who had been
All patients in this study showed at least one clinical symptom that has been associated with HPP in other studies.[4,5,27] as musculoskeletal symptoms increase in the elderly population, it is somewhat problematic to attribute these symptoms completely to HPP in patients with only moderately reduced low ALP activity

Summary

Introduction

Hypophosphatasia (HPP) is a rare inherited disease caused by a loss of function mutation within the gene ALPL encoding the tissue nonspecific alkaline phosphatase (TNSALP).(1) Deficient alkaline phosphatase (ALP) activity leads to an accumulation of its substrates including pyridoxal‐5‐phosphate (PLP) and inorganic pyrophosphate (PPi). HPP is currently classified into six forms based on the age of onset of clinical manifestation and the severity of the disease: perinatal, benign perinatal, infantile, childhood, adult, and odontohypophosphatasia.[3] the perinatal and infantile forms are associated with severe reduction of mineralized bone and high mortality caused by respiratory failure, the adult form shows a highly variable clinical severity.[1] These patients suffer from fractures, osteomalacia, muscle pain, recurring headaches, and intra‐articular calcium PPi dehydrate crystal deposition (CPPD).(4,5) The severity of the clinical manifestation correlates with the accumulation of ALP substrates, in particular PLP.[5,6] Patients suffering from the adult form frequently present with recurrent stress fractures of the metatarsals and subtrochanteric or diaphyseal femoral fractures.[4,5,7,8] Most of these fractures are associated with slow and often delayed fracture healing and can progress to more complicated fractures. We report the effects of the osteoanabolic drug teriparatide on BME in 2 HPP patients

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