Effect of an Intermittent Weekly Dose of Human Parathyroid Hormone (1-34) on Osteoporosis: A Randomized Double-Masked Prospective Study Using Three Dose Levels

Abstract

To test the effect of amino-terminal peptide 1-34 of human parathyroid hormone (hPTH (1-34)) as a possible bone anabolic agent in the treatment of osteoporosis, weekly subcutaneous injection of 50 units (L group), 100 units (M group) or 200 units (H group) of hPTH (1-34) was started in 220 patients with osteoporosis at 71 institutions randomly divided into three groups in a double-masked system. Lumbar spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) increased by 0.6%, 3.6% and 8.1% after 48 weeks in groups L, M and H respectively, responses in groups M and H being significantly higher than in L (p<0.05, Mann-Whitney U-test). Since the coefficient of variation for lumbar spine measurement stayed at 1-2.5%, increases of 3.6% and 8.1% appeared significant. Metacarpal BMD and cortical thickness measured by radiogrammetry did not change significantly. Serum calcium decreased in each group and serum phosphorus decreased in groups M and H. Urinary calcium/creatinine decreased at the 12th week in group H and at the 24th and 48th weeks in groups M and L. Serum 25(OH) vitamin D and 1,25(OH)(2) vitamin D decreased in each group at the 48th week (p<0.05). Serum bone-type alkaline phosphatase was increased at the fourth week in groups H and M and decreased at the 48th week in group H. Urinary hydroxyproline, pyridinoline and deoxypyridinoline declined significantly in each group. Backache improved in 30-40% of each group. No serious adverse effects were found during the test period. Intermittent weekly injection of hPTH (1-34) increased lumbar BMD in osteoporosis, suggesting usefulness in the treatment of osteoporosis.

Raloxifene and teriparatide (hPTH 1-34) have complementary effects on the osteopenic skeleton of ovariectomized rats

“…Onceweekly administration of PTH(1-34) was shown previously to significantly increase bone mass in postmenopausal women with osteoporosis [21]. In that study, 100 and 200 units of PTH induced 3.6% and 8.1% increases in vertebral BMD, respectively, after 48 weeks of treatment.…”

Regulation of osteoblast differentiation by interleukin-11 via AP-1 and Smad signaling [Review]

“…Thus, daily nasal spray of PTH(1-34) gives a short Tmax, which increases bone formation markers and at the same time reduces bone resorption markers with net positive effect [35]. Similarly, weekly subcutaneous injections of PTH(1-34) causes an increase in bone formation markers with a reduction in bone resorption markers [36]. In contrast, although PTH-Fc fusion protein shows a long half-life, weekly or twice-weekly administration can give net anabolic effect on bone [37].…”

Changes in the contents of enzymatic immature, mature, and non-enzymatic senescent cross-links of collagen after once-weekly treatment with human parathyroid hormone (1–34) for 18 months contribute to improvement of bone strength in ovariectomized monkeys

“…A sham operation was conducted on animals in one group (SHAM), whereas all animals in the remaining three groups had both ovaries surgically removed 1 week before starting treatment (OVX groups). Two OVX groups were subcutaneously administered once-weekly hPTH(1-34) acetate (Asahi Kasei Pharma Corp., Tokyo, Japan), relative activity 3,300 U/mg [4], at doses of 1.2 μg/kg (low-PTH group) or 6.0 μg/kg body weight (high-PTH group). The administration was initiated immediately after the operation.…”

“…Daily selfadministered subcutaneous injection of human PTH (hPTH) (1-34) (teriparatide) increased bone mineral density (BMD) compared to a placebo in post-menopausal osteoporotic patients [3]. Fujita et al [4] reported in a multicenter clinical trial that once-weekly administration of hPTH (100 and 200 U/week) for 12 months in patients with osteoporosis significantly increased lumbar BMD by up to 3.6% and 8.1%, respectively, without increasing bone resorption.…”