Vitamin D Deficiency in Children Undergoing Vertical Expandable Prosthetic Titanium Rib Treatment.

BACKGROUND: Vitamin D deficiency is prevalent in the pediatric population and multiple risk factors have been identified. Low vitamin D levels can result in poor bone mineralization and have been associated with a significantly higher risk of forearm fracture in children. Vitamin D deficiency has also been associated with pediatric critical illness. The purpose of this study was to determine whether children undergoing vertical expandable prosthetic titanium rib (VEPTR) treatment have low vitamin D levels. METHODS: Patients undergoing VEPTR treatment at a single institution were prospectively enrolled (VEPTR). All patients either had a diagnosis of thoracic insufficiency syndrome (TIS), or were at risk of developing TIS secondary to progressive scoliosis or chest wall deformity. Exclusion criteria were patients with rickets and patients receiving vitamin D supplementation at the time of VEPTR insertion. A group of healthy children who presented with fractures during the winter season were used as controls (FX). Vitamin D status and risk factors for vitamin D deficiency were evaluated. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OH-D) <20 ng/mL and vitamin D insufficiency as serum 25-OH-D between 20 and 29 ng/mL. RESULTS: Twenty-eight VEPTR and 25 FX patients were compared. The average age was 8.6 years in the VEPTR group and 9.1 years in the FX group. Twenty VEPTR patients (71%) and 19 FX patients (76%) demonstrated low vitamin D levels. The average 25-OH-D level was 27.3 ng/mL in the VEPTR group and 25.4 ng/mL in the FX group. Patient characteristics and vitamin D levels were similar between the groups. No association was found between vitamin D status and sex, race, obesity, or multivitamin use. CONCLUSIONS: Low vitamin D levels are common in children undergoing VEPTR treatment. In our series, the prevalence of vitamin D deficiency in this patient population was similar to reported rates in the general pediatric population. Vitamin D status should be routinely monitored in children undergoing VEPTR treatment and supplementation should be initiated if necessary.

Denosumab treatment for fibrous dysplasia.

Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)-regulating protein, α-subunit of the Gs stimulatory protein (G(s) α). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF-κB ligand (RANKL) is a cell-surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross-linked C-telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases.