Treatment of osteoporosis in postmenopausal women
A good-quality systematic review (SR)2 reported 10 moderate- and good-quality randomised controlled trials (RCTs) (including seven double-blind RCTs) investigating the effectiveness of hPTH(1-34). One trial3 in this SR reported fracture risk as a primary outcome measure. The trial compared hPTH(1-34) to calcium in postmenopausal women, reporting a reduction in risk of new vertebral fractures for hPTH(1-34) 20 μg per day (relative risk [RR]: 0.35, 95% confidence interval [CI]: 0.22–0.55). The absolute risk reduction (ARR) for vertebral fractures was 9% and ARR for non-vertebral fractures was 3% (RR: 0.47, 95% CI: 0.25–0.88) for hPTH(1-34) 20 μg per day. Six moderate to good quality RCTs reported in the SR2 compared PTH to placebo or an active comparator and reported BMD as an outcome measure. Trials were for 1–3 years. Participants treated with hPTH(1-34) 20 µg per day had significant increases ranging from 9.7–10.3% in lumbar spine BMD and increases of 2.8–3.9% for FN BMD.
Treatment of osteoporosis in men
In a good-quality trial, men with idiopathic osteoporosis (n = 23) were randomly assigned to hPTH(1-34) 25 μg versus placebo.4 After 18 months, BMD had increased significantly by 13.5% and 2.9% at the lumbar spine and FN respectively. Total-hip BMD did not change significantly, but there was a significant decrease of 1.2% at the one-third distal radius. Another good-quality trial was conducted in men with low BMD who were predominantly hypogonadal (n = 437).5 Participants were treated with 20 μg or 40 μg of hPTH(1-34) versus placebo with calcium and vitamin D. After one year, lumbar spine BMD increased by 5.4% with 20 μg, compared with no change with placebo. There was no significant difference in the fracture rate with hPTH(134) compared with the placebo.5
Combination with anti-resorptive therapies in postmenopausal osteoporosis
There is strong evidence that combination therapy with alendronate and teriparatide may in fact blunt the anabolic effect of teriparatide on BMD.2 There are no fracture data comparing the effect of the combination of teriparatide and alendronate with that of teriparatide alone.2 A recent open-label RCT has compared the effect on BMD between teriparatide and denosumab alone, or in combination. At 24 months, combination treatment increased BMD at the lumbar spine and hip more than either treatment alone; the study was not powered to detect an effect on fracture rate.9
An increased risk of osteosarcoma was reported in a lifelong carcinogenicity study involving Fischer rats given high-dose hPTH(1-34) from infancy through senescence (eight weeks to two years of age).7 Osteosarcoma was found with all doses and, in the lower dose ranges, was first detected after about 20 months of therapy. There have been no reports of osteosarcoma in clinical trial subjects, and conversely, after seven years of the Osteosarcoma Surveillance Study (an ongoing 15-year surveillance study initiated in 2003), there have been no osteosarcoma patients who have reported prior exposure to teriparatide.8 Although there are isolated case reports of osteosarcoma in patients with long-standing hyperparathyroidism, there is no evidence to suggest that osteosarcoma is of increased frequency in hyperparathyroidism. Nine trials investigating hPTH(1-34) reported post-dose hypercalcaemia (serum calcium level above 2.6 mmol/L) that ranged from 3–11% among patients taking hPTH(1-34) 20 μg compared with 0–3% among those taking the comparator.2 These episodes were mild, with serum calcium levels usually returned to normal within 24 hours and no clinical sequelae. There were no reported increases in renal stones. hPTH(1-34) 20 μg was associated with a significant increase in the proportion of patients experiencing dizziness (3%) and leg cramps (range 2–8%).