Work

8251 The Silent Thief: Neurofibromatosis Type 1 (NF1) Leading to Severe Osteoporosis and Recurrent Bone Fractures

Year: 2024

Type: article

Abstract: Disclosure: D.H. Sacoto: None. K. Madani: None. D. Patel: None. A. De Rosairo: None. G. Rai: None. A.A. Franco-Akel: None. R. Belokovskaya: None. Introduction: NF1 is an autosomal dominant disorder known to cause a remarkable reduction in bone mineral density (BMD) with almost a fivefold increase in fracture risk. Since fractures are associated with a high disability burden, early identification, prompt treatment, and consideration of prophylactic measures are important. We present a case of NF1 complicated with osteoporosis and recurrent bone fractures. Case presentation: An 85-year-old female with a history of NF1 complicated with a malignant left ankle Peripheral Nerve Sheet Tumor came in after a mechanical fall. Vital signs were stable. Examination demonstrated short stature, widespread cutaneous neurofibromas, and café au lait macules. Complain of generalized bone pain, in addition, to diffuse osseous demineralization on imaging and mild alkaline phosphatase elevation (141 U/L), led to further investigation, which revealed osteomalacia due to severe vitamin D deficiency (9.8 ng/mL) in the setting of malnutrition (albumin:3.4 mg/dL). Otherwise, normal renal function, phosphorus (3.7mg/dL) and calcium corrected for albumin (8.9 mg/dL). Previous records identified a right humerus close proximal fracture three years ago. At that time, a DEXA scan demonstrated severe osteoporosis with a lumbar T-score of -4.8 and dual femur of -3.7. She was started on Vitamin D supplementation, with questionable compliance. Bisphosphonates and denosumab were not prescribed due to the lack of guidelines on NF1 population. During the last two years, she experienced three more fractures, including a left femoral greater trochanteric, right 8th rib, and non-displaced pubic ramus fractures. One month ago, unfortunately, it expired due to septic shock. Discussion: Osteoporosis is found in 20–50% of NF1 patients, and it is associated with reduced serum 25-hydroxyvitamin D primarily due to a reduced expression of Vitamin D Receptor on neurofibromas in addition to reduced sun exposure and poor physical activity. At the molecular level, the loss of neurofibromin function causes a pathological increase in intracellular Ras activity, leading to an induction of osteoclastic activity and inhibition of osteoblastic differentiation. Currently, NF1 patients are resistant to bisphosphonate-induced apoptotic signals, and there are no guidelines for the use of denosumab in NF1 with osteoporosis. However, a recent clinical trial involving 141 NF1 adults identified that weight-bearing exercise, optimizing calcium and 25-hydroxyvitamin D intake and increased sun exposure can minimize BMD loss. However, guidelines for the management of bone abnormalities in NF1, including earlier screening and prophylactic therapy with vitamin D, are needed. Presentation: 6/3/2024

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvae163.519