Subtrochanteric and diaphyseal femoral fractures in hypophosphatasia-not atypical at all.

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.
Introduction: 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.
Methods: 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.
Results: 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%).
Conclusions: 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.