Emerging Therapies for the Treatment of Osteoporosis

Overview

Journal J Midlife Health

Date 2014 Mar 28

PMID 24672186

Citations 18

Authors

Garima Bhutani

Mahesh Chander Gupta

Affiliations

Soon will be listed here.

Abstract

Osteoporosis is a chronic disease of the osseous system characterized by decreased bone strength and increased fracture risk. It is due to an imbalance in the dynamic ongoing processes of bone formation and bone resorption. Currently available osteoporosis therapies like bisphosphonates, selective estrogen receptor modulators (SERMs), and denosumab are anti-resorptive agents. Parathyroid hormone analogs like teriparatide are the only anabolic agents currently approved for osteoporosis treatment. The side-effects and limited efficacy of the presently available therapies has encouraged extensive research into the pathophysiology of the disease and newer drug targets for its treatment. The novel anti-resorptive agents being developed are newer SERMs, osteoprotegerin, c-src (cellular-sarcoma) kinase inhibitors, αVβ3 integrin antagonists, cathepsin K inhibitors, chloride channel inhibitors, and nitrates. Upcoming anabolic agents include calcilytics, antibodies against sclerostin and Dickkopf-1, statins, matrix extracellular phosphoglycoprotein fragments activin inhibitiors, and endo-cannabinoid agonists. Many of these new drugs are still in development. This article provides an insight into the emerging drugs for the treatment of osteoporosis.

Citing Articles

Ponicidin Treatment Improved the Cell Proliferation, Differentiation, and Calcium Mineralization on the Osteoblast-Like MG-63 Cells.

Zhang Y, Hao P, Li H, Miao B Appl Biochem Biotechnol. 2022; 194(9):3860-3870.

PMID: 35556208 DOI: 10.1007/s12010-022-03927-3.

The Role of Cannabinoids in Bone Metabolism: A New Perspective for Bone Disorders.

Saponaro F, Ferrisi R, Gado F, Polini B, Saba A, Manera C Int J Mol Sci. 2021; 22(22).

PMID: 34830256 PMC: 8621131. DOI: 10.3390/ijms222212374.

Exploring the Potential Use of Peels as a Source of Cosmeceutical Sunscreen Agent for Its Antioxidant and Photoprotective Properties.

Vijayakumar R, Abd Gani S, Zaidan U, Halmi M, Karunakaran T, Hamdan M Evid Based Complement Alternat Med. 2020; 2020:7520736.

PMID: 32454871 PMC: 7222543. DOI: 10.1155/2020/7520736.

Association of Receiving Multiple, Concurrent Fracture-Associated Drugs With Hip Fracture Risk.

Emeny R, Chang C, Skinner J, OMalley A, Smith J, Chakraborti G JAMA Netw Open. 2019; 2(11):e1915348.

PMID: 31722031 PMC: 6902800. DOI: 10.1001/jamanetworkopen.2019.15348.

A Clinical Study of a Standardized Extract of Leaves of (Roxb ex DC) in Postmenopausal Osteoporosis.

Meeta , Raut A, Agashe S, Wajahat A, Sarada C, Vaidya A J Midlife Health. 2019; 10(1):37-42.

PMID: 31001055 PMC: 6459066. DOI: 10.4103/jmh.JMH_22_19.

References

Wells G, Cranney A, Peterson J, Boucher M, Shea B, Robinson V . Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev. 2008; (1):CD004523. DOI: 10.1002/14651858.CD004523.pub3. View

Eastell R, Reid D, Vukicevic S, Ensrud K, LaCroix A, Thompson J . Effects of 3 years of lasofoxifene treatment on bone turnover markers in women with postmenopausal osteoporosis. Bone. 2012; 50(5):1135-40. DOI: 10.1016/j.bone.2012.02.004. View

Moen M, Keam S . Denosumab: a review of its use in the treatment of postmenopausal osteoporosis. Drugs Aging. 2010; 28(1):63-82. DOI: 10.2165/11203300-000000000-00000. View

Hannon R, Clack G, Rimmer M, Swaisland A, Lockton J, Finkelman R . Effects of the Src kinase inhibitor saracatinib (AZD0530) on bone turnover in healthy men: a randomized, double-blind, placebo-controlled, multiple-ascending-dose phase I trial. J Bone Miner Res. 2009; 25(3):463-71. DOI: 10.1359/jbmr.090830. View

Ho M, Chen Y, Liao H, Chen C, Hung S, Lee M . Simvastatin increases osteoblasts and osteogenic proteins in ovariectomized rats. Eur J Clin Invest. 2009; 39(4):296-303. DOI: 10.1111/j.1365-2362.2009.02092.x. View

Kimura S, Nakagawa T, Matsuo Y, Ishida Y, Okamoto Y, Hayashi M . JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats. Eur J Pharmacol. 2011; 668(1-2):331-6. DOI: 10.1016/j.ejphar.2011.07.015. View

Murphy M, Cerchio K, Stoch S, Gottesdiener K, Wu M, Recker R . Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab. 2005; 90(4):2022-8. DOI: 10.1210/jc.2004-2126. View

Padhi D, Jang G, Stouch B, Fang L, Posvar E . Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2010; 26(1):19-26. DOI: 10.1002/jbmr.173. View

Henriksen K, Gram J, Schaller S, Dahl B, Dziegiel M, Bollerslev J . Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II. Am J Pathol. 2004; 164(5):1537-45. PMC: 1615650. DOI: 10.1016/S0002-9440(10)63712-1. View

10.

Ke H, Richards W, Li X, Ominsky M . Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012; 33(5):747-83. DOI: 10.1210/er.2011-1060. View

11.

Hayashibara T, Hiraga T, Yi B, Nomizu M, Kumagai Y, Nishimura R . A synthetic peptide fragment of human MEPE stimulates new bone formation in vitro and in vivo. J Bone Miner Res. 2004; 19(3):455-62. DOI: 10.1359/JBMR.0301263. View

12.

Afzal F, Polak J, Buttery L . Endothelial nitric oxide synthase in the control of osteoblastic mineralizing activity and bone integrity. J Pathol. 2004; 202(4):503-10. DOI: 10.1002/path.1536. View

13.

Gallagher J, Sai A . Molecular biology of bone remodeling: implications for new therapeutic targets for osteoporosis. Maturitas. 2010; 65(4):301-7. PMC: 2834801. DOI: 10.1016/j.maturitas.2010.01.002. View

14.

. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994; 843:1-129. View

15.

Kostenuik P, Ferrari S, Pierroz D, Bouxsein M, Morony S, Warmington K . Infrequent delivery of a long-acting PTH-Fc fusion protein has potent anabolic effects on cortical and cancellous bone. J Bone Miner Res. 2007; 22(10):1534-47. DOI: 10.1359/jbmr.070616. View

16.

Kumar S, Matheny C, Hoffman S, Marquis R, Schultz M, Liang X . An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation. Bone. 2009; 46(2):534-42. DOI: 10.1016/j.bone.2009.09.028. View

17.

Waalen J . Current and emerging therapies for the treatment of osteoporosis. J Exp Pharmacol. 2016; 2:121-34. PMC: 4863293. DOI: 10.2147/JEP.S7823. View

18.

Goldstein S, Duvernoy C, Calaf J, Adachi J, Mershon J, Dowsett S . Raloxifene use in clinical practice: efficacy and safety. Menopause. 2008; 16(2):413-21. DOI: 10.1097/gme.0b013e3181883dae. View

19.

Adamska M, MacDonald B, Sarmast Z, Oliver E, Meisler M . En1 and Wnt7a interact with Dkk1 during limb development in the mouse. Dev Biol. 2004; 272(1):134-44. DOI: 10.1016/j.ydbio.2004.04.026. View

20.

Kendler D, Palacios S, Cox D, Stock J, Alam J, Dowsett S . Arzoxifene versus raloxifene: effect on bone and safety parameters in postmenopausal women with osteoporosis. Osteoporos Int. 2011; 23(3):1091-101. DOI: 10.1007/s00198-011-1587-0. View