Adult Hypophosphatasia Treated with Teriparatide: Report of 2 Patients and Review of the Literature

Camacho, Pauline M.; Mazhari, Alaleh; Wilczynski, Cory; Kadanoff, Ruth; Mumm, Steven; Whyte, Michael P.

doi:10.4158/ep15890.or

Cited by 46 publications

(32 citation statements)

References 12 publications

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“…The most recent study also reported some benefit for 2 adult female HPP patients . Interestingly, all patients who have been treated with teriparatide have been woman . Our study is therefore the first to report the effects of teriparatide on male adult patients.…”

Section: Discussionsupporting

confidence: 56%

“…Yet, it is not clear whether this could be explained by an inefficacy of the drug or by noncompliance of the patient. The most recent study also reported some benefit for 2 adult female HPP patients . Interestingly, all patients who have been treated with teriparatide have been woman .…”

Section: Discussionmentioning

confidence: 93%

“…Hence, there is yet no approved medical therapy for adult‐onset HPP patients in Europe and North America, who had no symptoms in childhood or adolescence. Off‐label use of teriparatide has first been reported in adults in 2007, and showed variable clinical effects in further studies . In 2017, the treatment of 8 adult HPP patients with a monoclonal antisclerostin antibody (BPS804) increased lumbar BMD and bone formation markers, but no data on fracture healing or BME were presented.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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The 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

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Recombinant parathyroid hormone is not approved in children due to their growing skeleton and the known risk of osteosarcoma in rats [114]. Case reports of recombinant parathyroid hormone (PTH 1-34, Teriparatide) administration to postmenopausal females with HPP display serologic evidence of a rise of ALP and decrease of inorganic metabolites, significant reduction of pain, and/or improvement of bone mineral density [115][116][117]. In case reports, teriaratide therapy has been titrated to serologic and clinical markers (for example low/suppressed ALP and/or elevated ALP substrates), pain severity, and fracture frequency.…”

Section: Treatmentmentioning

confidence: 97%

Hypophosphatasia: Review of Bone Mineral Metabolism, Pathophysiology, Clinical Presentation, Diagnosis, and Treatment

Meah

Basit

Emanuele

et al. 2016

Clinic Rev Bone Miner Metab

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Hypophosphatasia (HPP) is a rare, inherited form of rickets or osteomalacia due to reduced activity of tissue non-specific alkaline phosphatase (TNSALP) caused by a loss of function mutation in the TNSALP gene marked by a low serum alkaline phosphatase. The ratio of PPi to Pi is crucial in the mineralization process. This process is regulated by the interaction of three phosphatases present in matrix vesicles: the mineralization promotors TNSALP and phosphatase orphan 1 (PHOSPHO1) and the mineralization inhibitor nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1). HPP is seen worldwide affecting all races. The broad-ranging clinical severity of HPP is correlated to the pattern of inheritance and degree of TNSALP activity, with lower levels of activity seen in the more severe autosomal recessive forms. HPP is marked by compromise of phase 2 hydroxyapatite crystal formation beyond the matrix vesicle resulting in skeletal hypomineralization, spontaneous fractures, tooth loss, and chondrocalcinosis. The major forms in declining order of severity include the following: perinatal, infantile, childhood, and adult HPP in addition to OdontoHPP and benign prenatal HPP. Biochemistry typically reveals a low serum alkaline phosphatase and elevated alkaline substrates such as pyridoxal-5′-phosphate (PLP) and phosphoethanolamine (PEA). Asfotase alfa, a recent novel enzyme replacement therapy for the treatment of HPP, has transformed this once lethal disease to one that is less severe.

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“…Timely diagnosis and treatment of HPP can reduce the risk of serious complications, such as those experienced by this patient. There is currently no approved treatment available for adult- © C I C E d i z i o n i I n t e r n a z i o n a l i onset HPP, though there is some evidence to support the use of teraparatide in this cohort (4,20,21). The use of bisphosphonates in this disease is not advised, as this treatment can exacerbate the already dysfunctional bone turnover in HPP (22,23).…”

Section: Minor Featuresmentioning

confidence: 99%

Adult-onset hypophosphatasia diagnosed following bilateral atypical femoral fractures in a 55-year-old woman

Lawrence

Saeed

Bartlett

et al. 2017

ccmbm

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SummaryWe report the case of a 55-year-old woman who presented to the emergency department having woken from sleep with right sided thigh swelling. Pelvic radiographs revealed bilateral atypical subtrochanteric femoral fractures (ASFFs). In the two years leading up to this admission, the patient had experienced gradually increasing pain and weakness in her legs which had resulted in a decrease in her mobility from fully mobile to bed-bound. During this time a neurologist had organised a magnetic-resonance imaging (MRI) scan of the brain and spine which was normal. There was no history of bisphosphonate (BP) use. Historical and admission blood tests revealed a persistently low serum alkaline phosphatase (ALP), with all other results within normal limits. The patient was treated with intramedullary nailing of both femurs and histological analysis of bone reamings were characteristic of hypophosphatasia (HPP). The patient was independently mobilising with a walking frame on discharge. Subsequent genetic testing revealed bi-allelic pathogenic variants in the TNSALP gene: c.526G>A, p.(Ala176Thr) and c.1171C>T, p.(Arg391Cys). HPP is an inborn error in metabolism caused by mutation in the gene coding for tissue non-specific alkaline phosphatase (TNSALP), resulting in a decrease in serum ALP concentrations. The age at which it presents which can vary from childhood to middle age, with symptoms ranging from perinatal death to late-onset osteomalacia. In those patients who survive to adulthood, there is a predisposition to fractures, including ASFFs. Treatment with asfotase alfa (a bone-targeted, recombinant human TNSALP) has been approved for perinatal, infantile and paediatric-onset hypophosphatasia.This case emphasises the importance of viewing persistent low ALP as a 'red flag' in patients presenting with musculoskeletal symptoms. Timely diagnosis and treatment of HPP can reduce the risk of serious complications, such as those experienced by this patient.

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Adult Hypophosphatasia Treated with Teriparatide: Report of 2 Patients and Review of the Literature

Cited by 46 publications

References 12 publications

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

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

Hypophosphatasia: Review of Bone Mineral Metabolism, Pathophysiology, Clinical Presentation, Diagnosis, and Treatment

Adult-onset hypophosphatasia diagnosed following bilateral atypical femoral fractures in a 55-year-old woman

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