Forsteo ® (teriparatid)

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Forsteo® (teriparatid): Verkningsmekanism

Daglig administrering av teriparatide stimulerar företrädesvis osteoblastic aktivitet över osteoklastisk aktivitet, vilket resulterar i ny benbildning.

Mechanism of Action

Endogenous 84-amino-acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidney. Forsteo (rhPTH(1-34)) is the active fragment (1-34) of endogenous human parathyroid hormone. Physiological actions of PTH include stimulation of bone formation by direct effects on bone forming cells (osteoblasts) indirectly increasing the intestinal absorption of calcium and increasing the tubular re-absorption of calcium and excretion of phosphate by the kidney.1

Pharmacodynamic Effects

Forsteo is a bone formation agent to treat osteoporosis. The skeletal effects of Forsteo depend upon the pattern of systemic exposure. Once-daily administration of Forsteo increases apposition of new bone on trabecular and cortical bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity.1

Further information

New bone formation is observed on the trabecular and cortical (periosteal and/or endosteal) bone surfaces.2

Structural histomorphometric analyses conducted on iliac crest biopsies from PMW with osteoporosis revealed that teriparatide improved

 

  • trabecular bone volume,

  • trabecular bone connectivity,

  • structure model index, and

  • cortical thickness.3

Dynamic histomorphometric analyses conducted on iliac crest biopsies from PMW with osteoporosis demonstrated that teriparatide stimulates bone formation on all bone envelopes (cancellous, endocortical, intracortical, and periosteal) as early as 3 months and remains sustained for the full 24 months of therapy.4,5

Radionuclide bone scan imaging has demonstrated a direct metabolic effect of teriparatide on the whole skeleton and various subskeletal sites.6

New bone formed during teriparatide treatment has lower, more heterogeneous, mineral content, a property consistent with younger bone age.7

References

1. Forsteo [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3. Jiang Y, Zhao JJ, Mitlak BH, et al. Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res. 2003;18(11):1932-1941. https://doi.org/10.1359/jbmr.2003.18.11.1932

4. Dempster DW, Zhou H, Recker RR, et al. A longitudinal study of skeletal histomorphometry at 6 and 24 months across four bone envelopes in postmenopausal women with osteoporosis receiving teriparatide or zoledronic acid in the SHOTZ trial. J Bone Miner Res. 2016;31(7):1429-1439. http://dx.doi.org/10.1002/jbmr.2804

5. Dempster DW, Zhou H, Recker RR, et al. Differential effects of teriparatide and denosumab on intact PTH and bone formation indices: AVA osteoporosis study. J Clin Endocrinol Metab. 2016;101(4):1353-1363. http://dx.doi.org/10.1210/jc.2015-4181

6. Moore AE, Blake GM, Taylor KA, et al. Changes observed in radionuclide bone scans during and after teriparatide treatment for osteoporosis. Eur J Nucl Med Mol Imaging. 2012;39(2):326-336 http://dx.doi.org/10.1007/s00259-011-1974-y

7. Dempster DW, Roschger P, Misof BM, et al. Differential effects of teriparatide and zoledronic acid on bone mineralization density distribution at 6 and 24 months in the SHOTZ study. J Bone Miner Res. 2016;31(8):1527-1535. http://dx.doi.org/10.1002/jbmr.2825

Glossary

PMW = postmenopausal women

Datum fӧr senaste ӧversyn 2020 M02 17

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