Bone microarchitecture and microfractures in disorganized bone in a young female with pycnodysostosis and atypical femur fractures: A case for novel fracture prediction technology using ALIGNOGRAM<sub>1.0</sub> analysis.
Authors
Affiliations (6)
Affiliations (6)
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: [email protected].
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia; Department of Endocrinology, Monash Health, Clayton, Victoria, Australia; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia.
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia; Department of Endocrinology, Monash Health, Clayton, Victoria, Australia.
- Department of Endocrinology and Diabetes, Alfred Health, Melbourne, Australia; School Public Health and Preventative Medicine, Monash University, Melbourne, Victoria, Australia.
- Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia; Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.
Abstract
Pycnodysostosis (PYCD) is a rare genetic bone disease characterized by impaired osteoclastic bone resorption. The inability to resorb bone leads to sclerosis, with increased bone mineral density (BMD) but paradoxically increased bone fragility. We report a case of a young female with PYCD with multiple fragility fractures including bilateral atypical femur fractures (AFF). Areal and volumetric bone density were supranormal, measured by dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), respectively. However, bone disorganization was prominent, observed on visual assessment of HR-pQCT images, with microfractures and sclerotic intramedullary lesions. ALIGNOGRAM<sub>1.0</sub> is an artificial intelligence (AI) powered disorganization quantifier. It detected femoral lesions (including microfractures) on femoral radiographs up to two years prior to atypical femoral fractures at those sites. These microcracks were not visible on routine hip radiographs without the ALIGNOGRAM<sub>1.0</sub> software. We postulate that disorganized bone, including microfractures, may be an underrecognized mechanism of bone fragility in patients with PYCD that could contribute to complications such as delayed fracture healing. Visual assessment via HR-pQCT may detect gross abnormalities but may miss subtle, subclinical changes - e.g., early sclerotic changes - that predate severe lesions and are not visible on routine HR-pQCT analysis. Quantitative tools such as ALIGNOGRAM<sub>1.0</sub> may be particularly valuable in disorders characterized by paradoxical skeletal fragility despite normal or elevated bone density and apparently preserved microarchitecture. By quantifying bone disorganization on standard radiographs, these approaches may provide complementary information beyond conventional assessments of bone mass and structure. The paradox of severe fragility despite supranormal bone density has long remained unexplained. This diagnostic paradox is not unique to pycnodysostosis and is encountered across a range of genetic, metabolic, and treatment-related skeletal disorders in which fracture risk appears disproportionate to conventional measures of bone density or structure. Consequently, there is a need for complementary approaches capable of identifying abnormalities that are not captured by standard assessments. In genetic and metabolic bone disorders (e.g., pycnodysostosis or hypophosphatasia) that evade conventional assessments of bone health (e.g., DXA and HR-pQCT), we demonstrate how disorganization may act as a causative mechanism as an independent biomarker of fragility.