An atypical subtrochanteric femoral fracture from pycnodysostosis: A lesson from nature

Yates, Christopher J; Bartlett, Miriam J; Ebeling, Peter R.

doi:10.1002/jbmr.308

Cited by 46 publications

(28 citation statements)

References 19 publications

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“…[11–14] Atypical femoral fractures are associated with high complication rates with operative fixation using conventional open reduction and internal fixation technique. [15] Several authors [16] have recommended the use of intramedullary nail systems for the management of atypical femoral fractures.…”

Section: Discussionmentioning

confidence: 99%

A case report of pycnodysostosis with atypical femur fracture diagnosed by next-generation sequencing of candidate genes

et al. 2017

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Rationale:Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, craniofacial dysmorphism, acro-osteolysis, osteosclerosis, and brittle bone with poor healing. Pycnodysostosis results from the deficient activity of cathepsin K, a lysosomal cysteine protease that is encoded by CTSK.Patient concerns:We report a Korean adult patient with pycnodysostosis and atypical femur fracture whose diagnosis was confirmed by next-generation sequencing (NGS) of candidate genes. A 41-year-old female patient was presented with a left femur fracture after falling down. Underlying sclerotic bone disease was suspected as a radiographic skeletal survey showed thickened cortical bones, and the total body bone density was increased (T score was 5.3, and Z score was 4.9).Diagnoses:We performed candidate gene sequencing of various sclerotic bone diseases for the differential molecular diagnosis of underlying sclerosing bone disease. Two heterozygous variants of CTSK were detected. One was a frameshift variant in exon 5, c.426delT (p.Phe142Leufs∗19), which was previously reported, and the other was a novel missense variant in exon 6, c.755G>A (p.Ser252Asn). Sanger sequencing of CTSK confirmed the 2 heterozygous variants and thus the patient was diagnosed with pycnodysostosis.Interventions:The patient had emergency surgery for subtrochantic femoral fracture.Outcomes:After 4 months of surgery, the patient had almost a full range of hip and knee movements and radiographs show the substantial bridging callus across the fracture.Lessons:Candidate gene sequencing could be a useful diagnostic tool for the genetically heterogeneous skeletal dysplasia group, especially in cases with a mild or atypical clinical phenotype.

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Section: Discussionmentioning

confidence: 99%

A case report of pycnodysostosis with atypical femur fracture diagnosed by next-generation sequencing of candidate genes

et al. 2017

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“…Although newer evidence suggests that AFFs are a form of stress fracture, their exact pathophysiology and relationship to bisphosphonate use are not well understood [1,5,9,10,14]. As AFFs have been associated with monogenetic diseases such as hypophosphatasia, X-linked hypophosphatemia, and pycnodysostosis, genetic differences could be a factor predisposing to formation of AFFs [15,16]. Because the mechanical strength of bone is dependent on both bone quality and bone geometry, hip geometry is thought to contribute to the risk of sustaining an AFF [7,9,[17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Bone cross-sectional geometry is not associated with atypical femoral fractures in Asian female chronic bisphosphonate users

Chou

Png

et al. 2015

Bone

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“…(3)(4)(5) Furthermore, ASFFs have been reported in additional heritable diseases of low bone turnoverosteopetrosis (6,7) and pycnodysostosis. (8) HPP is the inborn-error-of-metabolism characterized biochemically by low serum alkaline phosphatase (ALP) activity (hypophosphatasemia) and caused by loss-of-function mutation(s) within the gene that encodes the ''tissue-nonspecific'' isoenzyme of ALP (TNSALP). (9) Consequently, the natural substrates of this cell surface enzyme accumulate extracellularly (9) and include: (1) phosphoethanolamine (PEA), a component of the phosphatidylinositol-glycan linkage apparatus that couples some proteins to cells; (2) pyridoxal 5 0 -phosphate (PLP), the major circulating form of vitamin B 6 ; and (3) inorganic pyrophosphate (PPi), an inhibitor of mineralization and the ancestral molecule for the BPs.…”

Section: Introductionmentioning

confidence: 99%

“Atypical femoral fractures” during bisphosphonate exposure in adult hypophosphatasia

Sutton

Mumm

Coburn

et al. 2012

Journal of Bone and Mineral Research

156

126

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We report a 55-year-old woman who suffered atypical subtrochanteric femoral fractures (ASFFs) after 4 years of exposure to alendronate and then zolendronate given for ''osteoporosis.'' Before alendronate treatment, she had low bone mineral density. After several months of therapy, metatarsal stress fractures began. Bisphosphonate (BP) administration was stopped following the ASFFs, and the adult form of hypophosphatasia (HPP) was diagnosed from low serum alkaline phosphatase (ALP) activity, high endogenous levels of two natural substrates for the ''tissue-nonspecific'' isoenzyme of ALP (TNSALP), and a heterozygous mutation within the gene that encodes this enzyme. Experience with other HPP families showed that her mutation (Arg71His) with a second defective TNSALP allele can cause severe HPP in infancy, and when heterozygous can cause mild HPP featuring premature loss of deciduous teeth in children. Because the skeletal disease of HPP results from extracellular accumulation of the TNSALP substrate inorganic pyrophosphate (PPi) and its inhibitory effect on mineralization, perhaps HPP patients or carriers will have adverse effects from BPs. BPs are analogues of PPi and can suppress bone turnover but also deactivate TNSALP. Our report is the first of BP exposure preceding ASFFs in adult HPP. To explore a potential role for TNSALP deactivation in ASFFs, mutation analysis of TNSALP should be studied in a cohort of these patients. Meanwhile, clinicians must suspect HPP when clinical or laboratory clues include premature loss of primary dentition, pseudofractures or recurrent poorly healing metatarsal stress fractures, a family history suggestive of HPP, or low serum ALP activity. If HPP is documented, BP treatment might be avoided. To establish the diagnosis of HPP, assays for two natural substrates for TNSALP and TNSALP mutation analysis are available in commercial laboratories. With positive findings, radiological or bone biopsy evidence of acquired osteomalacia would indicate the adult form of this inborn-error-of-metabolism. ß

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An atypical subtrochanteric femoral fracture from pycnodysostosis: A lesson from nature

Cited by 46 publications

References 19 publications

A case report of pycnodysostosis with atypical femur fracture diagnosed by next-generation sequencing of candidate genes

A case report of pycnodysostosis with atypical femur fracture diagnosed by next-generation sequencing of candidate genes

Bone cross-sectional geometry is not associated with atypical femoral fractures in Asian female chronic bisphosphonate users

“Atypical femoral fractures” during bisphosphonate exposure in adult hypophosphatasia

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