Profound hypocalcemia following effective response to zoledronic acid treatment in a patient with juvenile Paget's disease.

Juvenile Paget's disease (JPD) is a rare, autosomal recessive osteopathy. Although it has phenotypic overlap with Paget's disease of bone (PDB), it is probably a distinct entity. Because of its rarity, optimal disease management has not yet been established by randomized controlled trials. However, clinical, biochemical, and radiographic improvement has been reported after treatment with antiresorptive agents, including calcitonin and bisphosphonates (BPs). Compared with other BPs, zoledronic acid (ZOL) has a higher affinity to bone mineral and is a stronger inhibitor of the enzyme farnesyl pyrophosphate synthase (the main target of nitrogen-containing BPs), properties that explain the prolonged effect of ZOL on bone turnover and render it a therapeutic option for JPD, similar to PDB. We describe hereby, for the first time in the literature, the case of a patient with JPD who developed severe hypocalcemia and secondary hyperparathyroidism following effective treatment with ZOL.

Dual-energy X-ray absorptiometry and quantitative ultrasound in patients with Paget's disease of bone before and after treatment with zoledronic acid: association with serum bone markers and Dickkopf-1.

The main aim of this study was to determine the effect of zoledronic acid (ZOL) on parameters of dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) in unaffected bones of patients with Paget's disease of bone (PDB). The secondary aim was the association of bone markers and Dickkopf (DKK)-1 with parameters of DXA and QUS. Ten consecutive patients with polyostotic PDB (median age: 63 yr) received a single 5-mg ZOL infusion. The patients were subjected to calcaneal QUS and DXA of both lumbar spine (LS) and femoral neck (FN). Blood samples for serum bone markers and DKK-1 were serially obtained for 12 mo. There was a significant increase in LS (p=0.005) and FN bone mineral density (BMD) (p=0.021) 12 mo after ZOL infusion. QUS parameters remained unaffected throughout the study. A significant correlation between broadband ultrasound attenuation and DKK-1 (p<0.001) and between speed of sound and DKK-1 (p=0.033) at baseline was found, which remained significant after adjustment for gender, age, and body mass index. Our data suggest that a single ZOL infusion significantly increases nonpagetic BMD 12 mo after treatment but has no effect on QUS parameters or DKK-1. Significant correlations were observed between QUS parameters and DKK-1 at baseline.

Serum homocysteine, folate and vitamin B12 in patients with Paget's disease of bone: the effect of zoledronic acid.

High serum homocysteine (HCY) and indirectly deficiency of folate and/or vitamin B(12) stimulate bone resorption and adversely affect collagen cross-linking. The aim of this study was the evaluation of serum levels of HCY, folate and vitamin B(12) in patients with Paget's disease of bone (PDB) and the effect of zoledronic acid (ZOL) on their serum levels. Nine consecutive patients with polyostotic PDB (median age 66 years) received a single 5-mg ZOL infusion. Blood samples for HCY, folate, vitamin B(12), 25-hydroxyvitamin D (25-OH-D), total serum alkaline phosphatase (TSAP), bone-specific serum alkaline phosphatase (BSAP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were obtained at baseline and 3, 6 and 12 months after ZOL infusion. Twelve age-, gender- and BMI-matched healthy individuals were recruited for the control group at baseline assessment. Patients with PDB had significantly higher serum HCY (p = 0.028), folate (p < 0.001) and bone markers [TSAP (p < 0.001), BSAP (p < 0.001) and CTX (p < 0.001)] compared with the control group at baseline. In the pagetic group, serum HCY significantly decreased 3 months after ZOL infusion and remained essentially unchanged up to the end of the study (p = 0.005). Serum vitamin B(12) and folate remained unaffected throughout the study. Our data suggest that serum HCY levels are increased in patients with PDB. A single ZOL infusion results in a decrease in HCY levels that might represent another mechanism for the reduction of the activity of PDB achieved by ZOL.