Therapy of hypoparathyroidism by replacement with parathyroid hormone

Abstract

Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL) seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT) possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range). Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone.

Figure 1

Results from a randomized controlled study on effects of PTH_1–84 replacement therapy versus conventional treatment on plasma ionized calcium levels. Patients in the placebo group received placebo injections in combination with conventional therapy (calcium supplements and activated vitamin D analogues). Data are stratified by whether patients at the end of study were managed on treatment with PTH alone (PTH only), PTH plus activated vitamin D (PTH + VitD), PTH plus activated vitamin D and calcium supplements (PTH + VitD + calcium), or placebo. The background light gray square indicates the reference range (1.18–1.32 mmol/l). Reproduced with permission from JBMR [17].

Figure 2

Diurnal variations in plasma ionized calcium levels in patients with hypoparathyroidism following 24 weeks of treatment with 100 μg of PTH_1–84 (black) (n = 21) or placebo (gray) (n = 17). The background light gray square indicates the reference range (1.18–1.32 mmol/l). The P value indicates significance between groups by repeated measurements ANOVA. Median with interquartile (25% to 75% percentile) range. ^▲ P < 0.01 and ^∗ P < 0.001 by post hoc comparison. Reproduced with permission from JBMR [18].

Figure 3

Diurnal variations in renal excretion of calcium (excretion per hour) in patients with hypoparathyroidism following 24 weeks of treatment with 100 μg of PTH_1–84 (black) (n = 21) or placebo (gray) (n = 17). P value indicates significance between group differences by repeated measurements ANOVA. ^▲ P < 0.01 by post hoc comparison. Reproduced with permission from JBMR [18].

Figure 4

Changes in areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) as assessed by DXA and QCT scans, respectively. Changes were assessed between baseline and 24 weeks of trial during which studied patients were treated with 100 μg of PTH_1–84 (read) or placebo (blue) [20].

Figure 5

Regions of the lumbar spine vertebra included in measurement of bone mineral density by DXA and QCT scans. In addition to the vertebral body, areal bone mineral density (aBMD) as assessed by DXA includes density measurement of the posterior processes (spinous process) as indicated by the background light gray square. Measurement of volumetric bone mineral density (vBMD) by QCT-scans includes only the central (trabecular) part of the vertebral body.