Osteoporosis – An Enormous Burden Worldwide 

Osteoporosis, a silent disease, is a pathological condition characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in bone fragility and increased risk of fracture.1 It is caused by an imbalance between bone formation and resorption, and can be influenced by several factors including age, sex, genetics, hormonal changes, and lifestyle choices.

Osteoporosis is a major concern globally, causing a fracture every 3 seconds.2 With India's aging population and longer life expectancy, the risk of osteoporosis is even higher.3

Breaking Down Osteoporosis Treatment

The primary goal of managing osteoporosis is to prevent fractures. There are two main categories of pharmacological agents available for treating osteoporosis: antiresorptive agents and anabolic agents. Antiresorptive agents reduce bone resorption by inhibiting osteoclast activity. Examples of these agents include bisphosphonates, estrogens, selective estrogen receptor modulators, strontium ranelate, and denosumab.Anabolic agents, which include Teriparatide and Abaloparatide, stimulate bone formation.

Head-to-head studies have shown that anabolic agents are more effective in reducing fractures and increasing bone density than antiresorptive drugs. However, the effects of anabolic agents are transient, and a transition to antiresorptive drugs may be necessary.4

Teriparatide: A Powerful Drug in Anabolic Therapy

Teriparatide, the first approved drug in the anabolic therapy category, is a powerful drug that stimulates new bone growth similar to parathyroid hormone. This medication is the first osteoporosis treatment that generates new bone with architecture resembling normal bone.a By enhancing bone microarchitecture and increasing bone mass, teriparatide substantially diminishes the risk of fractures.

Teriparatide exerts its beneficial effects on bone formation through two distinctive mechanisms. The first mechanism involves direct stimulation of bone formation within active remodelling sites (remodelling-based bone formation) and on the surfaces of previously inactive bone (modelling-based bone formation). The second mechanism is an increase in the initiation of new remodelling sites. 

Both mechanisms contribute to the final increase in bone density observed by non-invasive tools such as DXA.8

The Fracture Prevention Trial played a key role in getting FDA and EMA approval for teriparatide as the first anabolic agent for severe osteoporosis in postmenopausal women.5,6 Later, it was also approved for treating osteoporosis in both men and women at risk of fracture due to glucocorticoid therapy.7

Several clinical studies have confirmed the efficacy of teriparatide in reducing the risk of vertebral and non-vertebral fractures. In particular, teriparatide treatment at the FDA-approved dose of 20 μg/day has been found to reduce the risk of vertebral fractures by 65% (risk ratio [RR] 0.35, 95% CI 0.22–0.55) and decrease the risk of non-vertebral fractures by 53% (0.47, 0.25–0.88)9.

Hence, extensive real-world experience has also confirmed that teriparatide provides fracture and bone density benefits in post-menopausal osteoporosis, similar to those observed in clinical trials.b

Recently, in November 2020, the FDA approved changes to the teriparatide label, eliminating the 2-year lifetime treatment limitation and the boxed warning concerning the possible risk of osteosarcoma in humans treated with teriparatide. Notably, there is no evidence of an increased risk of osteosarcoma with the use of teriparatide.10

Conclusion:

Teriparatide reduces fracture risk by increasing bone mineral density, especially in the trabecular compartment. With the availability effective treatments like Teriparatide, there is hope for reducing the burden of osteoporotic fractures in the population.

References:

1. Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet. 2019 Jan 26;393(10169):364-376. 2.     Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006 Dec;17(12):1726-33. 3. Khadilkar AV, Mandlik RM. Epidemiology and treatment of osteoporosis in women: an Indian perspective. Int J Womens Health. 2015 Oct 19;7:841-50. 4.     Reid IR, Billington EO. Drug therapy for osteoporosis in older adults.Lancet. 2022;399(10329):1080-1092. 5.     Bodenner D, Redman C, Riggs A. Teriparatide in the management of osteoporosis. Clin Interv Aging. 2007;2(4):499-507. 6.     Lindsay R, Krege JH, Marin F, et al. Teriparatide for osteoporosis: importance of the full course. Osteoporos Int.2016;27(8):2395-410. 7.     FDA Approved Drug Products: FORTEO (teriparatide) injection, for subcutaneous use. 8. EMA Approved Drug Products: Sondelbay (teriparatide) Subcutaneous Injection. 9. Fenwick S, Vekariya V, Patel R, et al. Comparison of pharmacokinetics, pharmacodynamics, safety, and immunogenicity of teriparatide biosimilar with EU- and US-approved teriparatide reference products in healthy men and postmenopausal women, Osteoporos Int.2023;34(1):179-188. 10.  Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med.2001;344(19):1434-41. 11.  Hauser B, Alonso N, Riches PL. Review of Current Real-World Experience with Teriparatide as Treatment of Osteoporosis in Different Patient Groups. J Clin Med. 2021 Apr 1;10(7):1403. doi: 10.3390/jcm10071403. PMID: 33915736; PMCID: PMC8037129. 12.   Miller PD, Lewiecki EM, Krohn K, Schwartz E, et al. Teriparatide: Label changes and identifying patients for long-term use Cleve Clin J Med.2021;88(9):489-493.