Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Parathyroid hormone and analogues
General information
Both intact parathyroid hormone (e.g. PTH 1–34 , teriparatide) and smaller N-terminal fragments PTH 1–84 are used therapeutically. Recombinant PTH 1–34 is called teriparatide.
No adverse reactions have been reported with single infusions of up to 60 mg of synthetic human parathyroid hormone in diagnostic procedures [ , ]. Although bone resorption increases if the hormone is given continuously or in high doses, it has an anabolic effect on bone when given intermittently. Synthetic parathyroid hormone fragments have therefore been used in the treatment of slow turnover osteoporosis. However, no improvement in fracture risk has been documented, and the anabolic effect may only be present in the first 12 months [ ]. The use of parathyroid hormone in the treatment of hypoparathyroidism is also under investigation, with the optimum dosage and target calcium concentrations yet to be determined.
Reviews of parathyroid hormone have suggested that it is generally well tolerated [ ]. Adverse reactions to parathyroid hormone that have been reported in clinical trials are mild and include transient bone pain, nausea, dizziness and local irritation at the injection site [ ]. Hypercalcemia, which is common, is usually mild and asymptomatic.
Parathyroid hormone has potent anabolic effects on the skeleton if given intermittently; being used in clinical trials. Initial concerns about the development of osteosarcoma in rats after prolonged treatment with high doses of parathyroid hormone have not been confirmed in human trials, but surveillance continues [ ]. In one study there was a mild increase in creatinine, which was thought not to have clinical significance [ ]. Mild nausea [ ] and arthralgia [ , ] have also been reported.
Drug studies
Observational studies
Nausea was reported in 18% and headache in 13% of 552 women who took parathyroid hormone 40 micrograms, compared with 8% of the 544 women who took placebo [ ].
Women aged more than 45 years with low bone mineral density were randomized to hormone replacement therapy with (n = 90) or without (n = 90) 100 micrograms of subcutaneous PTH 1–84 [ ]. Those who received PTH 1–84 had more hypercalciuria (43%), hypercalcemia (14%), nausea (25%), vomiting (11%), and dizziness (10%). It was thought that they might not have had as great an increase in calcium concentrations as would have been expected, because of a tendency of hormone replacement therapy to lower calcium concentrations.
Combination studies
Generally, previous studies have shown a lack of effect of teriparatide if given in combination with bisphosphonates, and combination therapy is generally not recommended. Sequential therapy, starting bisphosphonates after treatment with teriparatide after 2 years, is generally recommended. In a 1-year partially double-blinded, randomized, study in postmenopausal women with osteoporosis, who used teriparatide alone, teriparatide + zoledronic acid, or zoledronic acid alone, adverse reactions within the first 3 days after infusion occurred at a rate of 69% with the combination, 58% with zoledronic acid, and 27% with teriparatide [ ]. After 3 days the rates were comparable across the three groups (85%, 88%, and 85%, respectively). There was hypercalcemia (predefined as serum calcium > 2.89 mmol/l) in one participant in the combination group and two in the teriparatide group. There were no reports of long-term adverse effects on renal function (comparing creatinine clearance values at baseline versus 12 months) in any group.
Systematic reviews
In a narrative review of teriparatide in the treatment of glucocorticoid-induced osteoporosis there were higher frequencies of nausea (RR = 2.3), abdominal cramps (RR = 3.2), and hypercalcemia (RR = 9.7) [ ].
In an 18-month open trial of teriparatide in patients with previous parathyroidectomy and a continued risk of osteoporosis, the most common adverse reactions were musculoskeletal symptoms, including muscle strains, aches, and pains. Other adverse reactions were nausea and redness and discoloration at the injection site [ ]. Teriparatide also appears to be associated with limb pain, which the European Medicines Agency noted to be “very common” [ ].
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here