A Case Report: Rare Cause of Recurrent Fragility Fracture in an Older Adult-Osteopetrosis

Case Description:

Case Report
A 68-year-old Malay woman, postmenopausal since age 40, had no significant health issues until the age of 54, when she began experiencing recurrent fragility fractures. In 2010, at age 54 years old, she sustained a left intertrochanteric femur fracture from a trivial fall, underwent proximal femoral nailing and was prescribed alendronate for one year. In 2019, at age 63, she sustained another left intertrochanteric fracture following a fall, necessitating replating surgery complicated by a surgical site infection. After completed antibiotics postoperatively, she regained ambulation with a walking frame. She required blood transfusion both admission in 2010 and 2019. An esophagogastroduodenoscopy (OGDS) in 2019 reveled gastritis, but no gastric or duodenal ulcers. She has never undergone a colonoscopy. In May 2024, she presented with left hip pain following a low-trauma fall while praying on an unstable chair. She reported no history of bleeding. The patient became edentulous by age 40, losing all her teeth progressively without seeking dental care. She denies hearing and vision impairments, toothaches, back pain, or constitutional symptoms. She is married, with one healthy daughter and has 16 siblings. One sister experienced recurrent hip fractures at age 60 and reported died in her 70s, was told due to “pancytopenia”.

Dual-energy X-ray absorptiometry (DXA) (Hologic): (Images: 1-3)
• Lumbar spine (L1-L4): T-score 15.2 with BMD 2.723 g/cm2 (however it has included vertebral pedicle, might affect the accuracy)
• Right neck of femur: T-score 11.4 with BMD 2.116 g/cm2
• Right distal forearm: T-score 5.9 with BMD 1.046 g/cm2

Radiographic Findings:
• Fracture of left neck of femur with evidence of an old healed intertrochanteric fracture and the presence of a proximal femoral nail. (Image 4)
• Left distal femur showed metaphyseal widening with a characteristic funnel-shape “Erlenmeyer-flask” deformity.
• Chest X-ray demonstrated generalized osteosclerosis, exhibiting a “marble bone” appearance, with normal heart shadow and clear lung fields. (Image 5)
• Thoracolumbar X-ray showed sclerosis and thickened endplates and scoliosis at L3-L4 and presence of characteristic “sandwich vertebrae” and “Ruggers-jersey” appearance. (Image 6)

Based on clinical, radiological along with consultation with a group of specialists (geriatrician, orthopedic surgeon and radiologist), a diagnosis of autosomal dominant osteopetrosis was established. A multidisciplinary meeting with patient and their family concluded that surgery carried a high risk due to osteopetrotic bone, so the neck of femur fracture was managed conservatively. Her hemoglobin level was 6.8g/dL and iron studies confirmed iron deficiency anemia. She received two units packed red cells and iron supplementations. Six months later, the patient is ambulating with a walking frame, is independent in daily activities, and reports no hip or jaw pain or further falls.

Discussion
In the study by Waguespack et al., a bimodal age distribution was observed with autosomal dominant osteopetrosis. The mean age at diagnosis was 3.8 years in children and 20.3 years in adults with less common cases diagnosed as late as the sixth decade of life. [1]
We reported a 68-year-old postmenopausal woman with recurrent falls and fragility fractures, initially misdiagnosed with osteoporosis and treated with alendronate for a year. This highlights the importance of considering alternative causes of fragility fractures, particularly when radiographic reveal significant bone abnormalities. Despite high bone mineral density and T score in DXA, the patient’s bones were fragile.
Radiograph findings were characteristic of osteopetrosis, including “Erlenmeyer flask” deformity, “sandwich vertebrae” and “Rugger-jersey’ spine”, although these features can overlap with hyperparathyroidism. (Her serum parathyroid hormone levels were normal)
She also had recurrent asymptomatic iron deficiency anemia, likely due to decreased marrow production and increased red blood cell destruction from splenomegaly. Osteomyelitis, a known complication of osteopetrosis postoperative, was absent in this case. Waguespack et al reported 16% incidence of osteomyelitis in adult in autosomal dominant osteopetrosis. [1]
Visual impairment, although rare in autosomal dominant osteopetrosis, was not observed in this patient. Waguespack et al reported a 19% incidence of visual impairment. [1]
The patient was advised to maintain regular dental care due to an increased risk of mandible osteomyelitis, dental caries and abscesses. Benichou et al. reported mandible osteomyelitis in 12.9% of cases, dental abscess in 9.7% and significant dental decays in 35.5%.[2]
Her neck of femur fracture was conservatively with pain control and physiotherapy, which improved her mobility. Surgical management of osteopetrosis-related fracture is challenging due to the brittle bones, increase intraoperative fracture risk, and complication such as thermal necrosis, hardware failure and infection. A review of 50 operations reported a 6% nonunion and infection rate. [3]

Conclusion
Misdiagnosing osteopetrosis as osteoporosis or using antiresorptive agents can lead to inappropriate management. Early detection is crucial for managing fragility fractures, facilitating timely interventions, reducing fall risk and ensure comprehensive multidisciplinary care. Osteopetrosis-related fragility fractures required special attention due to the heightened risk of surgical complications, nonunion and infection. Proactive detection and fall prevention strategies are essential to mitigating the socioeconomic impact of osteopetrosis-related fractures.

Credit:

We thank the medical staffs for their care, the patient and family for publication consent, and Dr. Oo Cheng Yeow for radiographic interpretation. Thanks to Dr Alan Pok Wen Kin, Dr Elizabeth Chong Gar Mit and Dr Rizah Mazzuin Razali from Geriatric Unit, Hospital Kuala Lumpur for proofreading this case report.

References:

1. S.G.Waguespack, S.L.Hui, L.A.DiMeglio and M.J.Econs, “Autosomal dominant osteopetrosis: clinical severity and natural history of 94 subjects with a chloride channel 7 gene mutation,” Journal of Clinical Endocrinology & Metabolism, 2007, 92 (3), 771-778.
2. Benichou O.D., Laredo J.D., de Vernejoul M.C., “Type II autosomal dominant osteopetrosis (Albers-Schonberg disease): clinical and radiological manifestations in 42 patients.” Bone, 2000,26:87-93.
3. H.Q. Ding, H.J. Chen, H.M. Lin, J.K Xu, Z.L. Huang, W.S Li and J. Hu, “Further understanding on osteopetrotic femoral fractures: a case report and literature review,” BMC Surgery, 2021,21:117.