Teriparatide effectiveness

Ettinger B, San Martin J, Crans G, Pavo I (2004) Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 19 745-751... 

Calcitonin is approved for use in the treatment of postmenopausal osteoporosis. It has been shown to increase bone mass and reduce fractures, but only in the spine. It does not appear to be as effective as bisphosphonates or teriparatide. 

Fig. 12.3 Effects of daily teriparatide (TPTD) administration on biomarkers of bone formation (bone ALP and PICP) and bone resorption (DPD/Cr and NTx/Cr) in postmenopausal women with osteoporosis. Changes in bone formation markers at 1 month were significantly correlated with improvements in bone structure after 22 months of treatment (from [48]). 

Two carcinogenicity bioassays were conducted in rats (3-60x MRHD). Treatment resulted in a marked dose-related increase in the incidence of osteosarcoma, a rare mahgnant bone tumor, in both male and female rats. Osteosarcomas were observed at all doses and the incidence reached 40-50% in the high-dose groups. Teriparatide also caused a dose-related increase in osteoblastoma and osteoma in both sexes. Bone tumors in rats occurred in association with a large increase in bone mass and focal osteoblast hyperplasia Second 2-year study was carried out in order to determine the effect of treatment duration and animal age on the development of bone tumors. Female rats were treated for different periods between 2 and 26 months of age (at 3x to 20x MRHD based on body surface area). The... 

In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a mahgnant bone tumor) that was dependent on dose and treatment duration. Effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times the exposure in humans given a 20 meg dose. 

As Mrs TY has only just been recently started on alendronate, she would not be eligible for teriparatide because, as yet, she has not had a treatment failure or experienced any side-effects from alendronate. She also has only one fracture so far. 

Although Mrs GG may not wish to take a bisphosphonate she may be persuaded to take calcium with or without vitamin D which is effective although less effective than a bisphosphonate. It is a cheaper and less toxic option. Other options such as teriparatide and strontium ranelate are more expensive and there is less experience in their use but they should be discussed with Mrs GG. 

The polypeptide parathormone is released from the parathyroid glands when the plasma Ca2+ level falls. It stimulates osteoclasts to increase bone resorption in the kidneys it promotes calcium reabsorption, while phosphate excretion is enhanced. As blood phosphate concentration diminishes, the tendency of Ca2+ to precipitate as bone mineral decreases. By stimulating the formation of vitamin D hormone, parathormone has an indirect effect on the enteral uptake of Ca2+ and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that, unlike parathormone, is effective orally. Teriparatide is a recombinant shortened parathormone derivative containing the portion required for binding to the receptor. It can be used in the therapy of postmenopausal osteoporosis and promotes bone formation. While this effect seems paradoxical in comparison with hyperparathyroidism, it obviously arises from the special mode of administration the once daily s.c. injection generates a quasi-pulsatile stimulation. Additionally, adequate intake of calcium and vitamin D must be ensured. 

Teriparatide (a recombinant PTH, residues 1 -34), which has been shown to be effective in osteoporosis. It acts like PTH and stimulates osteoblasts. It is used mostly for patients with established osteoporosis (who have already fractured), who have particularly low BMD or several risk factors for fracture, or who cannot tolerate the oral bisphosphonates. 

Drugs currently used to treat osteoporosis are classified into those that inhibit osteoclastic bone resorption (including bisphos-phonates, denosumab, and selective estrogen receptor modulators) and those that stimulate bone formation by osteoblasts (parathyroid hormone and derivatives, such as teriparatide). Strontium ranelate may have a dual effect. Other drugs being tested in clinical trials include inhibitors of cathepsin K (an osteoclastic enzyme critical for bone resorption) and of sclerostin (a negative modulator of the Wnt pathway) [21],... 

Teriparatide contains the first 34 amino acids in human parathyroid hormone and represents a novel approach to osteoporosis treatment. Although hyperparathyroidism leads to bone loss (see Fig. 88-3), therapeutic doses (for shorter periods of time) conversely improve BMD and rednce fractnre risk. Parathyroid hormone is currently the only approved osteoporosis medication that works by stimulating bone formation. Becanse of adverse effects and cost concerns, teriparatide is reserved for treating those at high risk of osteoporosis-related fracture who cannot or will not take or have failed bisphosphonate therapy. 

Clinical Effectiveness. Teriparatide works equally well in women and men with osteoporosis. Teriparatide has reduced the risk of new vertebral fractnres by 65% compared with placebo (actnal fracture incidence 5% vs. 14%, respectively) in postmenopausal women with osteoporosis and pre-existing fractures. New nonvertebral fracture risk was reduced by 53% (3% fractures with teriparatide vs. 6% fractures with placebo) with the 20-mcg/day dosage. Teriparatide can... 

Orwoll ES, Scheele WH, Paul S, et al. The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 2003 18 9-17. 

There have been some relatively new developments in the treatment of osteoporosis. Selective oestrogen receptor modulators, for example raloxifene mimic the inhibitory effects of oestrogen on osteoclasts. Teriparatide, which is a recombinant fragment of... 

Candidates for teriparatide treatment include women who have a history of osteoporotic fracture, who have multiple risk factors for fracture, or who failed or are intolerant of previous osteoporosis therapy. Teriparatide should not be used in patients who are at increased baseline risk for osteosarcoma (including those with Paget s disease of bone, unexplained elevations of alkaline phosphatase, open epiphyses, or prior radiation therapy involving the skeleton). Full-length PTH(l-84), which is in clinical trials, has not been associated with osteosarcomas. Other adverse effects have included exacerbation of nephrolithiasis and elevation of serum uric acid levels. 

Administered as a once-daily, 20-pg SC injection in the thigh or abdominal wall, teriparatide is a clear, colorless liquid that is available as a 750 pg/3 ml, prefilled, disposable pen that requires refrigeration. Concurrent calcium (1,000 mg) and vitamin D (400 lU) supplementation is recommended. Treatment for longer than 2 years is not recommended. Teriparatide is rapidly absorbed, demonstrates 95% bioavailability, and is quickly eliminated via both hepatic and extrahepatic routes. The half life is 1 hour when administered SC. Metabolic studies have not been performed on teriparatide however, the entire PTH preprohormone has been shown to undergo enzyme-mediated transformations in the liver. Dizziness and leg cramps are the most commonly reported adverse side effects. 

The effects of digitalis glycosides might be increased by rises in blood calcium levels, and the use of intravenous calcium may result in the development of potentially life-threatening digitalis-induced cardiac arrhythmias. Teriparatide appears not to affect the calcium-mediated pharmacodynamics of digoxin. 

Benson CT, Voelker JR, Teriparatide has no effect on the calcium-mediated pharmacodynamics of digoxin, Clin Pharmacol Ther (2003) 73, 87-94. 

Tumorigenidty Osteosarcoma is postulated as a potential adverse reaction to parathyroid hormone analogues, based on animal studies, and another case has been reported in a 67-year-old man who took teriparatide 20 micrograms/day subcutaneously for 2 months, 7 years after a course of radiotherapy for recurrent prostate cancer [65 ]. However, the osteosarcoma occurred within the field of previous radiotherapy and the time course suggested that the osteosarcoma may have been present before teriparatide administration. The authors noted that 430 000 patients have been treated with teriparatide for osteoporosis and that there have been only two reported cases of osteosarcoma, which is consistent with the expected population incidence of 4-5 per million. However, the effect of teriparatide on the growth of an undiagnosed osteosarcoma is unknown, and so teriparatide should be used with caution in patients who have had previous radiotherapy. 

Drag route of adntinistration Transdermal patches of teriparatide 20, 30, or 40 micrograms worn for 30 minutes/day have been compared with placebo patches and subcutaneous teriparatide 20 micrograms/day for 6 months in 165 women with osteoporosis [66. One patient withdrew because of skin hyperpigmentation and all had transient mild to moderate erythema at the patch site, with no difference between teriparatide and placebo patches. There were similar biochemical and skeletal effects in those who used the patches and subcutaneous teriparatide, including a small increase in serum calcium. 

Cosman F, Lane NE, Bolognese MA, Zanchetta JR, Garcia-Hemandez PA, Sees K, Matriano JA, Gaumer K, Daddona PE. Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2010 95(1) 151-8. 

Gamsjaeger, S. et al. (2011) Effects of one year daily teriparatide treatment on trabecular bone material properties in... 

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