Paget’s Disease of Bone and Calcium Homeostasis: Focus on Bisphosphonate Treatment

Abstract

Paget's disease of bone (PDB) is the second most common metabolic bone disease. Bisphosphonates (BPs) are currently the drugs of choice for PDB. PDB and osteomalacia are both common in the elderly. The concept of relative vitamin D deficiency in patients with PDB was suggested long ago, but it has not yet elucidated. Both diseases predispose to fractures, but their combined action to fragility has not been studied yet. The older BPs, mainly etidronate, further inhibit bone mineralization. Mineralization defects have also been described in patients with PDB treated with pamidronate. Moreover, hypocalcemia and secondary hyperparathyroidism after treatment with BPs have been described in PDB. Hypocalcemia seems to be more severe after treatment with the more potent, intravenous zoledronic acid, which is currently the treatment of choice for PDB. The counteracting hyperparathyroidism pathophysiologically intends to increase renal reabsorption of calcium and 1.25-dihydroxy vitamin D production and to stimulate osteoclasts in order to prevent long-term hypocalcemia. However, the effect of PTH on osteoclasts is, at least partly, restricted in patients taking BPs. Secondary hyperparathyroidism is a potentially detrimental condition, especially in patients already suffering from another bone disease. Serum calcium and vitamin D deficiency should be restored before BP treatment and calcium and vitamin D administration should be possibly continued for longer after achieving normocalcemia, which may shorten the duration of secondary hyperparathyroidism. QUICK SUMMARY: Mineralization defects and hypocalcemia with secondary hyperparathyroidism have been described in patients with Paget's disease of bone treated with bisphosphonates. Secondary hyperparathyroidism may be a potentially detrimental condition for patients with Paget's disease of bone.

Preclinical evidence of potential craniofacial adverse effect of zoledronic acid in pediatric patients with bone malignancies

“…Other preclinical studies and clinical observations have demonstrated that BPs, in particular alendronate and ZOL, delay or inhibit tooth eruption causing several dental abnormalities [14][15][16][17] and may, as in the juvenile Paget's disease of bone, exert an inhibitory effect on bone mineralization [18]. Such inhibition of mineralization has been observed for various BPs using calvaria osteoblast culture [19].…”

Paget�s disease population analysis within Rheumatology Outpatient of the ASL of Biella (Piedmont Region, Italy)

“…Bone scintigraphy proved to be an effective valuable tool for evaluation of disease activity in the presence of pain in subjects with values of total alkaline phosphatase in the normal range. This review highlights areas of increased uptake and intense osteometabolic persist after infusion therapy suggesting the real need for re-treatment intravenous bisphosphonates (19). The potency of the drug was higher than assumed and does not require a subsequent annual infusion, as is shown in the technical form, while demonstrating the importance of reevaluate patients even after 1 year to monitor their levels of calcium, phosphate and PTH and continuing integrating daily calcium and Vit D.…”

Effect of Zoledronic Acid Infusion Therapy in Paget’s Disease

“…Literatürde belirtildiği gibi, Paget hastalığında hipokalsemi ve ikincil hiperparatiroidizm sorun olarak karşımıza çıkmaktadır. Bu nedenle, tedaviden önce serum kalsiyum ve D vitamini düzeyi düzeltilmeli, tedaviden sonra normokalsemi sağlanıncaya dek kalsiyum, D vitamini desteğine devam edilmelidir (6).…”