Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age


Parathyroid hormone

Evidence statement

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%).

Grade: A

Recommendation 22
Teriparatide treatment is recommended to reduce fracture risk in postmenopausal women and men over the age of 50 with osteoporosis who have sustained a subsequent fracture while on anti-resorptive therapy, or in whom anti-resorptive therapy is contraindicated.

Parathyroid hormone (PTH) is approved in Australia in the form of hPTH(1-34), also known as teriparatide. PTH is also produced in the form of hPTH(1-84), not available in Australia. Teriparatide acts predominantly on osteoblasts to increase new bone formation on trabecular and cortical surfaces by preferentially stimulating osteoblastic bone formation over osteoclastic bone resorption. Teriparatide acts to increase the lifespan of osteoblasts by reducing osteoblast apoptosis and by inducing recruitment and formation of new osteoblasts. The bone-remodelling rate as well as the amount of bone deposited in each remodelling cycle is increased. Cancellous-bone connectivity, trabecular thickness and cortical width are increased, as is periosteal bone formation, which is responsible for increasing cortical width and producing an increase in bone size. Skeletal mass and bone strength are also increased.1
Teriparatide increases lumbar spine and femoral neck (FN) bone mineral density (BMD) and decreases vertebral and non-vertebral fractures in postmenopausal osteoporosis with prior fracture. Hip-fracture risk has not been assessed.2 Teriparatide has also been shown to improve new, worsening and moderate to severe back pain and reduce height loss in patients who have sustained one or more new vertebral fractures.3 Teriparatide increases
BMD at the lumbar spine and FN in men with osteoporosis, but there are no data on fractures in this population.4,5
Teriparatide is a costly medication with a recommended 18-month course duration. Teriparatide is now  reimbursed by the Pharmaceutical Benefits Scheme for severe osteoporosis in patients with a very high risk of fracture who have:

  • a BMD T-score of ≤–3.0 or less
  • had two or more fractures due to minimal trauma
  • experienced at least one symptomatic new fracture after at least 12-months continuous therapy with an antiresorptive agent at adequate doses.

Dizziness, leg cramps, nausea, injection reactions and headache are the most commonly described side effects, occurring in 5% or less of cases. These are generally mild and do not require treatment discontinuation. Mild transient hypercalcaemia has been noted, but monitoring serum calcium is not a requirement of therapy.2 Mild increases in uric acid without the development of acute gout and small increases in urinary calcium excretion without nephrolithiasis have been reported.6 Oncogenicity studies in rats treated with high doses of teriparatide of near lifetime duration resulted in an increased risk of osteogenic sarcoma.7 Surveillance of human osteosarcoma cases has found no relationship with teriparatide.8

  • Teriparatide is given as a daily subcutaneous injection via a multi-dose pen device.
  • Because of expense, teriparatide is generally restricted to patients at very high risk of fracture.
  • Due to increased background risk of osteosarcoma, teriparatide is not recommended for patients with Paget disease, prior skeletal irradiation, bony metastases or prior skeletal malignancies, and for those with metabolic bone diseases (other than osteoporosis) or pre-existing hypercalcaemia.
  • BMD decreases within 12 months of stopping teriparatide, unless followed by sequential treatment with an anti-resorptive drug.
  1. Dempster D, Cosman F, Parisien M, et al. Anabolic actions of parathyroid hormone on bone. Endocr Rev 1993;14(6):690–709.
  2. Cranney A, Papaioannou A, Zytaruk N, et al. Parathyroid hormone for the treatment of osteoporosis: A systematic review. CMAJ 2006;175(1):52–9.
  3. Neer R, Arnaud C, Zanchetta J, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344(19):1434–41.
  4. Kurland E, Cosman F, McMahon D, et al. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: Effects on bone mineral density and bone markers. J Clin Endoncrinol Metab 2000;85(9):3069–76.
  5. Orwoll E, Scheele W, Paul S, et al. The effect of teriparatide therapy on bone mineral density in men with osteoporosis. J Bone Miner Res 2003;18(1):9–17. [human parathyroid hormone (1–34)]
  6. Black D, Bilezikian J, Ensrud K, et al. One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N Engl J Med 2005; 353(6):555–65.
  7. Barbehenn EK, Lurie P, Wolfe SM. Osteosarcoma risk in rats using PTH 1–34. Trends Endocrinol Metab 2001;12(9):383.
  8. Andrews EB, Gilsenan AW, Midkiff K, et al. The US post-marketing surveillance study of adult osteosarcoma and teriparatide: Study design and findings from the first 7 years. J Bone Miner Res 2012;27(12):2429–37.
  9. Leder BZ, Tsai JN, Uihlein AV, et al. Two years of denosumab and teriparatide administration in postmenopausal women with osteoporosis (The DATA Extension Study): A randomised controlled trial. J Clin Endocrinol Metab. 2014;99(5):1694–700.
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