Efficacy and Safety of the Biosimilar Recombinant Human Parathyroid Hormone Cinnopar® in Postmenopausal Osteoporotic Women: A Randomized Double-blind Clinical Trial
AbstractAbstractBackground: Due to high cost and burden of osteoporosis, it is reasonable to focus on the reduction of fractures as the main goal of treatment. We compared the efficacy and safety of a new biosimilar recombinant human parathyroid hormone (CinnoPar®, CinnaGen, Iran) to the reference product (Forteo®, Eli Lilly, USA) in a randomized double-blind clinical trial (RCT).Methods: Overall, 104 osteoporotic postmenopausal women aged 45-75 yr were randomized to receive 20 µg daily subcutaneous injections of either Forteo® or CinnoPar® for 6-months from 2011-2012. Bone biomarkers were measured at baseline, and during first, third, and sixth month's follow-up along with lumbar spine, total hip, and femoral neck bone mineral density (BMD) assessment at the baseline and six months after that. The study was registered in Iranian registry of clinical trials under the registration number of IRCT138810121414N5. The endpoints were to compare bone biomarkers, BMD and drug safety between groups. Data analysis was performed using SPSS 11.Results: Age range of ninety-four patients who completed the study was 42-81 yr. Participants were divided into Forteo (45 subjects) and CinnoPar (49 subjects) groups. No significant difference in terms of bone biomarkers or BMD scores was shown between groups (P≥0.05). The most prevalent side effects were hypercalcemia and hypercalciuria without any significant statistical differences between groups.Conclusion: CinnoPar® can be considered as a good alternative therapy for Forteo® in postmenopausal osteoporotic women due to its comparable efficacy and safety properties.
NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001). Osteoporosis prevention, diagnosis, and therapy. JAMA, 285(6):785–795.
Facts and statistics, osteoporosis general (2017). https://www.iofbonehealth.org/facts-statistics
Larijani B, Moayyeri A, Keshtkar AA, et al (2006). Peak bone mass of Iranian population: the Iranian Multicenter Osteoporosis Study. J Clin Densitom, 9(3):367-74.
Maalouf G, Gannagé-Yared MH, Ezzedine J, et al (2007). Middle East and North Africa consensus on osteoporosis. J Musculoskelet Neuronal Interact, 7(2):131-43.
World Health Organization: WHO scientific group on the assessment of osteoporosis at the primary health care level (2004). Summary Meeting Report; Brussels, Belgium. 5–7 May 2004; http://www.who.int/chp/topics/Osteoporosis.pdf
Keramat A, Larijani B, Adibi H (2012). Risk factors for spinal osteoporosis as compared with femoral osteoporosis in urban Iranian womwn. Iran J Public Health, 41(10): 52–59.
Larijani B, Mohajeri Tehrani MR et al (2004). Osteoporosis, global and Iranian aspects. Iran J Public Health, 0(0):1–17.
Tabatabaei-Malazy O, Larijani B, Abdollahi M (2015). Targeting metabolic disorders by natural products. J Diabetes Metab Disord,14: 57.
Heshmat R, Tabatabaei-Malazy O, Abbaszadeh-Ahranjani S, et al (2012). Effect of vitamin D on insulin resistance and anthropometric parameters in type 2 diabetes; a randomized double-blind clinical trials. Daru, 20(1):10.
Tabatabaei-Malazy O, Salari P, Khashayar P, Larijani B (2017). New horizons in treatment of osteoporosis. Daru, 25(1):2.
No Author list (2010). Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause,17(1):25-54.
Hopkins RB, Goeree R, Pullenayegum E, et al (2011). The relative efficacy of nine osteoporosis medications for reducing the rate of fractures in post-menopausal women. BMC Musculoskelet Disord, 12: 209.
Krege JH, Lane NE, Harris JM, Miller PD (2014). PINP as a biological response marker during teriparatide treatment for osteoporosis. Osteoporos Int, 25(9): 2159-2171.
Potts JT (2005). Parathyroid hormone: past and present. J Endocrinol, 187(3):311–325.
Burch J, Rice S, Yang H, et al (2014). Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups. Health Technol Assess, 18 (11): 1-180.
Rosen CJ, Drezner MK, Mulder JE (2017). Parathyroid hormone therapy for osteoporosis. www.uptodate.com. Accessed 4 Feb 2017.
Schuiling KD, Robinia K (2011). Osteoporosis update. J Midwifery Women's Health, 56(6):615-27.
Komm BS, Morgenstern D, Yamamoto LA, Jenkins SN (2015). The safety and tolerability profile of therapies for the prevention and treatment of osteoporosis in postmenopausal women. Expert Rev Clin Pharmacol, 8(6):769-84.
Wheater G, Elshahaly M, Tuck SP et al (2013). The clinical utility of bone marker measurements in osteoporosis. J Transl Med, 11:201.
Hwang JS, Tu ST, Yang TS et al (2006). Teriparatide vs. calcitonin in the treatment of Asian postmenopausal women with established osteoporosis. Osteoporos Int, 17(3):373–378.
Kung AWC, Pasion EG, Sofiyan M, et al (2006). A comparison of teriparatide and calcitonin therapy in postmenopausal Asian women with osteoporosis: a 6‐month study. Curr Med Res Opin, 22(5):929–937.
Leder BZ, O’Dea LSL, Zanchetta JR, et al (2014). Effects of Abaloparatide, a Human Parathyroid Hormone-Related Peptide Analog, on Bone Mineral Density in Postmenopausal Women with Osteoporosis. J Clin Endocrinol Metab, 100(2):697-706.
Miyauchi A, Matsumoto T, Shigeta H et al (2008). Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study. J Bone Miner Metab, 26(6):624–634.
Black DM, Bouxsein ML, Palermo L, et al (2008). Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling. J Clin Endocrinol Metab, 93(6):2166-72.
Sethi BK, Chadha M, Modi KD et al (2008). Efficacy of teriparatide in increasing bone mineral density in postmenopausal women with osteoporosis–an Indian experience. J Assoc Physicians India, 56:418-24.
Recker RR, Bare SP, Smith SY, et al (2009). Cancellous and cortical bone architecture and turnover at the iliac crest of postmenopausal osteoporotic women treated with parathyroid hormone 1-84. Bone, 44(1): 113-119.
Han B, Copeland M, Geiser AG, et al (2007). Development of a highly sensitive, high-throughput, mass spectrometry-based assay for rat pro collagen type-1 N-terminal pro peptide (P1NP) to measure bone formation activity. J Proteome Res, 6(11):4218-29.
Zanchetta JR, Bogado CE, Cisari C, et al (2010). Treatment of postmenopausal women with osteoporosis with PTH(1-84) for 36 months: treatment extension study. Curr Med Res Opin, 26(11): 2627-2633.
JGlover S, Eastell R, V. McCloskey E, Rogers A, Garnero P (2009). Rapid and robust response of biochemical markers of bone formation to teriparatide therapy. Bone, 45(6): 1053-1058.
Yamamoto T, Tsujimoto M, Hamaya E, Sowa H (2013). Assessing the effect of baseline status of serum bone turnover markers and vitamin D levels on efficacy of teriparatide 20 μg/day administered subcutaneously in Japanese patients with osteoporosis. J Bone Miner Metab, 31(2):199–205.
Recker RR, Marin F, Ish-Shalom S, et al (2009). Comparative Effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Miner Res, 24(8):1358–1368.
Miller PD, Hattersley G, Riis BJ, et al (2016). Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA, 316(7):722-33.
Ishtiaq S, Fogelman I, Hampson G (2015). Treatment of post-menopausal osteoporosis: beyond bisphosphonates. J Endocrinol Invest, 38(1):13-29.
Chen p, Jerome CP, Burr DB, et al (2007). Interrelationships between bone microarchitecture and strength in ovariectomized monkeys treated with teriparatide. J Bone Miner Res, 22 (6): 841-848.
Ellegaard M, Jorgensen NR, Schwarz P (2010). Parathyroid hormone and bone healing. Calcif Tissue Int, 87(1): 1-13.
Noorani M, Larijani B, Heshmat R (2012). Comparison of the effectiveness of domestic commercial recombinant PTH (Forteo) in improving bone density in patients with osteoporosis. Iranian Journal of Diabetes and Metabolism, 11:494–503. In Persian.
Kanis JA, McCloskey EV, Johansson H et al (2013). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int, 24(1):23–57.
Harper KD, Krege JH, Marcus R, Mitlak BH (2007). Osteosarcoma and teriparatide? J Bone Miner Res, 22(2): 334.