Recombinant parathyroid hormone for hypoparathyroidism in children: a narrative review

Abstract

The conventional management of hypoparathyroidism in children involves the use of calcium and vitamin D analogs. This therapy effectively increases the serum calcium levels but worsens hypercalciuria and its consequences such as nephrocalcinosis and renal insufficiency. Although replacement with the missing parathyroid hormone (PTH) is ideal and available for more than 2 decades, the reported concerns of osteosarcoma prohibited its use in children with open epiphyses. Nevertheless, the data accumulated over the past several years suggests that the fears of bone malignancies were probably overstated. With an aim to review the available data on recombinant PTH (rhPTH) use, we performed a literature search using international databases and identified 15 studies involving approximately 70 children with hypoparathyroidism due to various etiologies who received rhPTH1-34 for durations between 1 day and 13.5 years. All the studies appear to indicate that rhPTH1-34 therapy is an effective short and long-term strategy for treatment of hypoparathyroidism with better metabolic control, lesser effects on renal function and improved quality of life as compared to conventional therapy. A more significant conclusion is the safety of long-term use of rhPTH1-34 with no observed adverse skeletal effects so far. However, all studies mention the importance of a continued surveillance for adverse effects in the treated patients. This narrative review discusses the experience of rhPTH1-34 use exclusively in children.

Ten-year use of recombinant parathyroid hormone for the treatment of hypoparathyroidism in a boy with partial Jacobsen syndrome

“…Several recent studies have reported experience with rhPTH1 -34 and recommend the use of rhPTH1 -34 in adults as well as children for management of chronic HPT [10][11][12][13][14]. A recent review that included short and long-term experience on the use of rhPTH1 -34 in 70 children suggested rhPTH1 -34 to be an effective therapy for HPT that improves metabolic control and quality of life and is associated with better renal outcome in children with HPT [5]. Other reassuring features in our patient were a normal BMD after 10 years of PTH therapy, probably indicating a normal trajectory of bone accrual, and the attainment of height within the genetic potential.…”

“…The use of rhPTH1 -34 is prohibited in children with open epiphyses due to concerns of osteosarcoma reported in animal studies that led to black box warning Table I. by the FDA [5]. We monitored bone turnover by estimation of serum ALP at each clinic visit in addition to specific enquiries about any bone-related symptoms.…”

“…The conventional treatment of chronic HPT with calcium and vitamin D analogs poses a significant risk of hypercalciuria, nephrocalcinosis, and renal impairment [ 5 ]. Patients often require additional therapies such as thiazide diuretics and phosphate binders in order to prevent long-term complications [ 5 ].…”

“…The conventional treatment of chronic HPT with calcium and vitamin D analogs poses a significant risk of hypercalciuria, nephrocalcinosis, and renal impairment [ 5 ]. Patients often require additional therapies such as thiazide diuretics and phosphate binders in order to prevent long-term complications [ 5 ]. Although replacement therapy with recombinant human parathyroid hormone (rhPTH 1–34 ) has physiological benefits, it is rarely used in pediatric practice due to the FDA’s black box warning [ 5 ].…”

“…Patients often require additional therapies such as thiazide diuretics and phosphate binders in order to prevent long-term complications [ 5 ]. Although replacement therapy with recombinant human parathyroid hormone (rhPTH 1–34 ) has physiological benefits, it is rarely used in pediatric practice due to the FDA’s black box warning [ 5 ]. In this report, we describe our decade-long experience of treating HPT with rhPTH 1–34 in a boy with JS.…”