Teriparatide in osteoporosis

Medically Reviewed By : Dr Sravya, MBBS, MS

Introduction

Clinical trials have demonstrated the effectiveness of teriparatide in reducing both vertebral and non-vertebral fractures in post-menopausal and glucocorticoid-induced osteoporosis. With the widespread adoption of teriparatide over the past two decades, there is now a substantial body of real-world experience in routine clinical practice.

However, limited experience has been reported regarding the use of teriparatide in pre-menopausal osteoporosis or in combination with other therapies. Surveillance studies have not identified any safety concerns or signals indicating a possible association between teriparatide and osteosarcoma. Furthermore, this review examines the evidence for predicting response to teriparatide, aiming to provide insights into the optimal utilization of teriparatide within an increasingly diverse range of available treatments for osteoporosis.

In This Article

What is teriparatide

Teriparatide is an injection used to treat diseases which effect the bones and results in weakness in bones and break easily a condition called osteoporosis. It is used in both women and men who are in a condition of high risk of bone features and unable to do any other treatments. The formulation of the injection is that it contain a hormone called parathyroid hormone (PTH),it is a natural hormone and it works by causing the body in building new bones and works on increasing bone strength and density (thickness ).

How is the medicine should be used

The injection is coming as a solution which is applied under the skin specially in area of thigh or lower stomach area. The preciscribed dose is once a day for 2 years.
You can also inject ourselves or with a friend. Read the manual as user.
The packet will have a 28 doses along with a pen for injection. It is not recommended to use syringe.If needed use a new needle for each time when it is used.
The injection will not cure the osteoporosis rather control

Precaution taken before having teriparatide injection

Inform doctor about your allergic condition if you are allergic to any kind of medicine and ask the pharmacist and list all the ingredients included.
Inform your doctor about any history of bone diseases, including Paget's disease, bone cancer, or metastatic cancer to the bone, as well as prior radiation therapy targeting the bones. Additionally, disclose any conditions associated with excessive blood calcium levels, such as parathyroid gland disorders, kidney or urinary tract stones, and liver, kidney, or heart diseases.
Please be aware that teriparatide injection is intended for use in postmenopausal women who are no longer capable of becoming pregnant or breastfeeding. It is important to avoid using teriparatide injection during pregnancy or while breastfeeding.
It is important to be aware that teriparatide injection may lead to symptoms such as rapid heartbeat, dizziness, lightheadedness, and fainting, especially when transitioning from a lying position to standing up. These effects are more frequently experienced at the beginning of teriparatide injection usage. To mitigate this issue, it is recommended to rise slowly from lying down, allowing your feet to rest on the floor for a few minutes before standing up fully. It is advisable to have a nearby chair when administering teriparatide injection, ensuring that you have a place to sit down if you feel dizzy.

Mechanism of action of teriparatide

Parathyroid hormone (PTH) is a naturally occurring hormone that plays a vital role in regulating calcium and phosphate levels in the body, particularly in the bones and kidneys. It influences bone metabolism, the reabsorption of calcium and phosphate in the kidneys, and the absorption of calcium in the intestines. PTH exerts its effects by binding to specific receptors known as PTH receptors. When there is an excess of PTH, such as in conditions like hyperparathyroidism, it can lead to increased activity of osteoclasts and accelerated bone resorption. Interestingly, the effects of PTH on bone depend on the dosage and pattern of exposure. Continuous exposure to PTH promotes bone resorption, while intermittent exposure to low doses of PTH can stimulate bone formation more favorably than resorption.

Likewise, the effects of teriparatide on the skeletal system are influenced by its systemic exposure pattern.

When teriparatide is administered once daily, it stimulates the formation of new bone on various bone surfaces, including trabecular and cortical bone, through the preferential activation of osteoblastic activity over osteoclastic activity.
Teriparatide achieves its osteoanabolic effects by binding to PTH type 1 receptors (PTH type 1R), which are G-protein coupled receptors found on different cell types, including osteoblasts, osteocytes, and renal tubular cells.
By binding to PTH receptors on osteoblasts, teriparatide triggers signaling pathways involving protein kinase A (PKA) and protein kinase C (PKC), which promote anabolic effects on bone.
For instance, teriparatide increases the production of pro-osteoclastogenic cytokines like receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor. It also enhances the transcriptional expression of growth factors that support osteoblast activity, such as insulin-like growth factor 1 (IGF1) and fibroblast growth factor 2 (FGF2). Teriparatide also decreases the production of sclerostin, a negative regulator of bone formation, and facilitates the differentiation of osteoblasts

Know side effects

It is uncommon to experience side effects while using teriparatide; however, if they do occur, they are usually temporary and short-lived.

Currently known side effects include joint pain, headache, dizziness, and depression. Please note that as ongoing research progresses, the list of known side effects may be subject to change. For more detailed information on each side effect and suggestions for alleviating symptoms, please refer to the teriparatide factsheet.

It is important to mention that other symptoms and side effects may be listed in your patient information leaflet. These side effects were reported by patients participating in research trials, but it is unclear whether they were directly caused by teriparatide. It is worth noting that some of these side effects were also reported by patients receiving a placebo (inactive treatment).

Teriparatide in Post-Menopausal Osteoporosis

Clinical trials involving post-menopausal women have consistently shown that teriparatide (TPTD) is effective in improving bone mineral density (BMD) and reducing clinical fractures when compared to placebo.

Currently the only comparative study that specifically investigated the incidence of fractures as the primary outcome and confirmed that teriparatide significantly reduces the risk of vertebral fractures in post-menopausal osteoporosis. However, no significant reduction in non-vertebral fractures was observed .

Teriparatide in Pre-Menopausal Osteoporosis

Teriparatide is not officially approved for the treatment of pre-menopausal osteoporosis; however, there have been several reports on its outcomes in this patient population. In a pilot study involving 21 women with idiopathic osteoporosis and an average age of 39, teriparatide demonstrated anabolic effects. Over a period of 18 to 24 months, there was an average increase of 9.8% in spine bone mineral density (BMD). However, it is important to note that 19% of the women in the study did not respond to the treatment [33]. This is noteworthy as bisphosphonate therapy is generally not recommended for women of childbearing potential.
Unfortunately, a follow-up study conducted with the same cohort revealed a 4.8% decline in lumbar spine BMD, although a more modest decline was observed in the hip [34]. These findings led the authors to conclude that premenopausal women treated with teriparatide should be considered for anti-resorptive therapy after completing teriparatide treatment, particularly for those over the age of 40 who exhibited greater bone loss.

Teriparatide in Men

Severe osteoporosis can have equally devastating consequences for men, if not more so, compared to women [43,44]. In fact, over a third of men (37.1%) who experience a hip fracture will unfortunately pass away within the first year following the fracture, which is a significantly higher rate compared to women within the same time frame (26.4%) [43].
Although real-world experience with the use of teriparatide in men suggests a reduction in vertebral fractures, further clinical trials and real-world studies are needed to fully understand the efficacy of teriparatide in men. It is crucial that future clinical trials aim to accurately represent the real-world population in terms of age demographics, as this will contribute to a more comprehensive understanding of teriparatide's effectiveness in men.
Undoubtedly, there is a pressing need for additional studies on osteoporosis treatment in men, accompanied by regular review of medication licensing, in order to address this important healthcare issue.

Conclusion

Current real world experience confirms that Teriparatide (TPTD) treatment effectively reduces the risk of vertebral and non-vertebral fractures in postmenopausal women and in men,
Observational data also confirms that TPTD effectively reduces the risk of hip fractures by about 50%
This experience supports a move to first-line use of Teriparatide in patients at high risk of vertebral fractures, with strong evidence to justify this approach in post-menopausal osteoporosis.
Looking at various patient groups, TPTD may be more effective in younger patients compared to patients over however, this finding may be confounded by case selection and the fact that older patients have more comorbidities which can influence fracture risk.
Similarly, combination treatment, although not licensed, may be used more commonly in clinical practice for difficult cases in future and the collection of observational data will help to understand better whether and when to consider a combination approach. Given the limited experience in premenopausal women and for combined TPTD therapy, no recommendation for its use in these settings can be made.