Subtrochanteric and diaphyseal femoral fractures in hypophosphatasia—not atypical at all
- 11 Downloads
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.
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.
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.
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%).
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.
KeywordsAtypical femoral fractures Bisphosphonates Femoral geometry Hypophosphatasia
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.
This study is a retrospective evaluation of clinical routine data. For this type of study, formal consent is not required.
- 1.Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster DW, Ebeling PR, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Howe TS, van der Meulen MCH, Weinstein RS, Whyte MP (2014) Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 29(1):1–23CrossRefPubMedGoogle Scholar
- 15.Miyakoshi N, Aizawa T, Sasaki S, Ando S, Maekawa S, Aonuma H, Tsuchie H, Sasaki H, Kasukawa Y, Shimada Y (2015) Healing of bisphosphonate-associated atypical femoral fractures in patients with osteoporosis: a comparison between treatment with and without teriparatide. J Bone Miner Metab 33(5):553–559CrossRefPubMedGoogle Scholar
- 16.Gomberg SJ, Wustrack RL, Napoli N, Arnaud CD, Black DM (2011) Teriparatide, vitamin D, and calcium healed bilateral subtrochanteric stress fractures in a postmenopausal woman with a 13-year history of continuous alendronate therapy. J Clin Endocrinol Metab 96(6):1627–1632CrossRefPubMedGoogle Scholar
- 17.Huang HT, Kang L, Huang PJ, Fu YC, Lin SY, Hsieh CH, Chen JC, Cheng YM, Chen CH (2012) Successful teriparatide treatment of atypical fracture after long-term use of alendronate without surgical procedure in a postmenopausal woman: a case report. Menopause 19(12):1360–1363CrossRefPubMedGoogle Scholar
- 19.Sonohata M, Mawatari M, Hotokebuchi T, Okubo T, Ono H (2011) Bipolar hip arthroplasty for subtrochanteric femoral nonunion in an adult with autosomal dominant osteopetrosis type II. J Orthop Sci 16(5):652–655Google Scholar
- 20.Birmingham P, McHale KA (2008) Case reports: treatment of subtrochanteric and ipsilateral femoral neck fractures in an adult with osteopetrosis. Clin Orthop Relat Res 466(8):2002–2008Google Scholar
- 30.Saita Y, Ishijima M, Mogami A, Kubota M, Baba T, Kaketa T, Nagao M, Sakamoto Y, Sakai K, Kato R, Nagura N, Miyagawa K, Wada T, Liu L, Obayashi O, Shitoto K, Nozawa M, Kajihara H, Gen H, Kaneko K (2014) The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment. Bone 66:105–110CrossRefPubMedGoogle Scholar
- 34.Cundy T, Michigami T, Tachikawa K, Dray M, Collins JF, Paschalis EP, Gamsjaeger S, Roschger A, Fratzl-Zelman N, Roschger P, Klaushofer K (2015) Reversible deterioration in Hypophosphatasia caused by renal failure with bisphosphonate treatment. J Bone Miner Res 30(9):1726–1737CrossRefPubMedGoogle Scholar
- 37.Whyte MP, Zhang F, Wenkert D, McAlister WH, Mack KE, Benigno MC, Coburn SP, Wagy S, Griffin DM, Ericson KL, Mumm S (2015) Hypophosphatasia: validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients. Bone 75:229–239CrossRefPubMedGoogle Scholar