Case Report: Denosumab Improves Bone Mineral Density in Patient With Williams Syndrome and Osteoporosis

USA, Missouri, St. Louis
A 12-year-old Japanese girl with Williams syndrome and osteoporosis presented with very low bone mineral density and received treatment with denosumab.

Denosumab was found to improve the bone mineral density (BMD) in a 12-year-old patient with Williams syndrome and osteoporosis, according to a case report published in Journal of Medical Case Reports.

Patients with Williams syndrome most commonly have decreased BMD, which increases their risk for fractures. Currently, there are no established management therapies for osteoporosis in this patient population. 

Authors of a case report evaluated the efficacy of denosumab in improving BMD in a 12-year-old patient with Williams syndrome and osteoporosis.

Denosumab is considered off-label use in pediatric patients, and consent was obtained from the patient and patient’s parents before administering the medication.

The patient was diagnosed with Williams syndrome at the age of 2 years and was referred for osteoporosis treatment. She presented with decreased BMD values at lumbar and total hip, aortic stenosis that did not require surgery, and underwent corrective surgery for scoliosis at the age of 12 years. The patient also had mildly decreased reflexes at the extremities but had normal muscle strength. No previous fractures or family history of osteoporosis were reported.

Starting at 2 months after corrective surgery for scoliosis, denosumab was subcutaneously administered every 6 months. Bone turnover markers and BMD values were examined before initiating treatment and at 5, 9, 17, 12, and 29 months of treatment.

Serum tartrate-resistant acid phosphatase 5b (TRACP-5B) greatly decreased after the first administration of denosumab. The authors of the report also noted reduced serum bone-specific alkaline phosphatase (BAP), type I procollagen N-terminal propeptide (PINP), whole parathyroid hormone (PTH), and 1-alpha, 25-dihydroxy vitamin D3 levels. Urinary type I collagen amino-terminal telopeptide (NTX) and 25-hydroxyvitamin D3 were increased. No hypocalcemia was observed.

At 29 months, BMD for lumbar and total hip increased by 51.6% and 37.6%, respectively. No fractures or falls were reported, and the patient was able to be physically active without getting out of shape during the treatment period.

Limitations of the report included the sample size and limited data on the long-term effects of denosumab on Williams syndrome and osteoporosis.

Authors concluded, “To the best of our knowledge, this is the first experience with denosumab treatment in [patients with] Williams syndrome with osteoporosis. Based on our findings, denosumab may be an effective treatment option for [patients with] Williams syndrome with osteoporosis.”


Uehara M, Nakamura Y, Suzuki T, Sakai N, Takahashi J. Efficacy of denosumab therapy for a 12-year-old female patient with Williams syndrome with osteoporosis and history of fractures: a case report. J Med Case Rep. 2021;15(1):594. doi:10.1186/s13256-021-03175-9