Bone Health and Osteoporosis: Pharmaceuticals for Stronger Bones

Introduction
Understanding bone health
Osteoporosis: The silent threat
Pharmaceutical solutions for bone health
Pharmaceuticals and their efficacy
Conclusion
References
Further reading


Various pharmaceuticals are crucial in managing osteoporosis, a condition characterized by weakened bones. These medications are designed to improve bone health by slowing down bone loss, increasing bone density, and reducing fracture risk.

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Introduction

Maintaining good bone health is critical as strong bones provide a foundation for the body, support mobility, protect vital organs, and store essential minerals like calcium. Osteoporosis is a prevalent bone disease that significantly endangers bone health.

According to the World Health Organization (WHO), this disease has affected over 200 million people globally. In 2010, around 10.2 million people aged 50 years or older were diagnosed with osteoporosis in the United States alone, with the majority being women. Moreover, 43.3 million other individuals had low bone mass. The incidence of osteoporosis varies widely across continents, with Africa reporting the highest prevalence at 39.5%.

Osteoporosis results in weakened bones and an elevated fracture risk. Pharmaceuticals, including bisphosphonates, selective estrogen receptor modulators (SERMs), recombinant antibodies, and synthetic hormones, are crucial in managing bone density for osteoporosis.

Understanding bone health

Bones are crucial elements of the musculoskeletal structure, enabling support, defense, and body movement. They are continually changing tissues that undergo consistent remodeling throughout life. The fundamental anatomy of bones comprises a tough external layer designated cortical bone and a porous interior layer known as trabecular bone. The external layer facilitates strength and protection, while the interior layer aids metabolic functions and bone marrow production.

Bones serve vital functions such as supporting and structuring the body, protecting organs, facilitating movement with muscles and joints, storing minerals, and promoting hematopoiesis.

Optimal bone health depends on a balanced intake of essential nutrients, including calcium, vitamin D, magnesium, phosphorus, and vitamin K. Regular physical activity is crucial in preventing bone weakness. Both nutrition and exercise greatly affect hormonal balance, which is implicated in osteoporosis development during menopause or certain medical conditions.

Detrimental lifestyle factors such as smoking or excessive alcohol consumption can cause poor bone health by reducing bone density through various mechanisms. Osteoporosis frequently follows from these behaviors and can result in bone fractures, diminished mobility, persistent pain, and an overall decline in quality of life.

Osteoporosis: The silent threat

Osteoporosis is a bone disease characterized by decreased bone mineral density and bone mass, along with structural and strength alterations of the bone, which increase the risk of fractures. It is typically referred to as a "silent disease" since there are usually no apparent symptoms, and individuals may not be aware of the condition until they have experienced a fracture, which often occurs in the hip, wrist, or vertebrae in the spine.

Osteoporosis is typically diagnosed by assessing bone mineral density, commonly measured with dual-energy X-ray absorptiometry (DXA) technology. Results from the DXA test are reported as T-scores, where a score of -2.5 or below signifies osteoporosis.

Several factors have been identified as increasing the risk of developing osteoporosis, including natural declines in bone density over time that come with aging; gender, particularly in postmenopausal women when estrogen levels drop; genetic variations in genes involved in bone formation and resorption; a family history of osteoporosis; hormonal imbalances;  medical conditions like rheumatoid arthritis, celiac disease, or inflammatory bowel disease; and long-term usage of corticosteroids.

As previously stated, smoking, drinking alcohol, and having a sedentary lifestyle also increase the likelihood of developing osteoporosis.

Pharmaceutical solutions for bone health

There are several pharmaceutical options available for enhancing bone strength and treating osteoporosis. These options include medications, supplements, and treatments.

Bisphosphonates, such as alendronate, risedronate, and zoledronic acid, are commonly prescribed medications for osteoporosis. They work by inhibiting bone resorption reducing the activity of osteoclasts. SERMs, such as raloxifene, mimic the effects of estrogen in bones, helping to maintain its density.

Teriparatide is a synthetic form of parathyroid hormone (PTH) that stimulates new bone formation. It is administered as a daily injection and is used for severe osteoporosis.

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Denosumab is a monoclonal antibody targeting the protein RANKL, which acts as the primary signal to promote bone resorption.   This way, it inhibits osteoclast activity. Another monoclonal antibody is Romosozumab.

It works as a sclerostin inhibitor, promoting osteoblast differentiation. Supplements like calcium and vitamin D are crucial for maintaining bone health and preventing osteoporosis, with calcium supplements being most effective when taken alongside vitamin D to aid in calcium absorption.

Treatments for osteoporosis include hormone replacement therapy (HRT), which replaces declining hormones in postmenopausal women, and physical therapy and exercise programs that improve balance, strength, and posture to reduce the risk of falls and fractures. These interventions aim to decrease bone resorption, promote bone formation, and improve calcium and vitamin D levels, ultimately slowing down bone loss.

Pharmaceuticals and their efficacy

The effectiveness of pharmaceutical interventions for enhancing bone health and treating osteoporosis has been well-established. Medications such as bisphosphonates, teriparatide, and SERMs show better outcomes in bone mineral density, while medications such as denosumab show better behavior in reducing the risk of fracture/incidence. It is important to note that their administration will depend on the patient's severity, and they target different pathways in bone metabolism.

Only Romosozumab works to induce bone formation from all the available therapeutic approaches, which is its major advantage compared to other medications. However, it is important to consider potential side effects and individual comorbidities when prescribing these pharmaceuticals.

In 2021, the National Institute of Health and Care Excellence in the EU stopped recommending Romosozumab for severe osteoporosis treatment due to its suspected association with a higher incidence of heart attacks and strokes. Earlier this year, researchers from Bristol Medical School suggested that the side effects could be attributed to decreased sclerostin levels. The study demonstrated a 30% increased risk of heart attacks among individuals with genetic variants predisposed to lower levels of sclerostin.

Conclusion

Healthcare professionals must evaluate risks, benefits, side effects, and patient factors when considering treatments. The best example is Romosozumab, a medication of great advancement that promotes bone formation compared to other treatment approaches. However, concerns about its association with heart attacks and strokes require careful consideration, emphasizing the significance of personalized medicine.

References

  • Denosumab. Uses, Interactions, Mechanism of Action | DrugBank Online. (n.d.) [Online] https://go.drugbank.com/drugs/DB06643 (Accessed on October 2023)
  • Johnson M. L, et al. (2009). How genomics has informed our understanding of the pathogenesis of osteoporosis. Genome Medicine, 1(9), 84. https://doi.org/10.1186/gm84
  • Patel D, et al. (2023). A narrative review of the pharmaceutical management of Osteoporosis. Annals of Joint, 8, 25–25. https://doi.org/10.21037/aoj-23-2
  • Romosozumab – StatPearls – NCBI Bookshelf. (n.d.) [Online] https://www.ncbi.nlm.nih.gov/books/NBK585139/ (Accessed on October 2023)
  • ROS comments on NICE decision not to recommend new osteoporosis treatment. (n.d.). [Online] https://theros.org.uk/healthcare-sector-news/ros-comments-on-nice-decision-not-to-recommend-new-osteoporosis-treatment/ (Accessed on October 2023)
  • Salari N, et al.(2021). The global prevalence of osteoporosis in the world: A comprehensive systematic review and meta-analysis. Journal of Orthopaedic Surgery and Research, 16(1). https://doi.org/10.1186/s13018-021-02772-0
  • Study provides genetic evidence on new osteoporosis drug heart attack risk. (2023) [Online] https://www.bristol.ac.uk/alspac/news/2023/osteoporosis.html (Accessed on October 2023)

Further Reading

  • All Osteoporosis Content
  • Bone Disease
  • What is Osteoporosis?
  • Osteoporosis Symptoms
  • Osteoporosis in Men
More…

Last Updated: Nov 3, 2023

Written by

Deliana Infante

I am Deliana, a biologist from the Simón Bolívar University (Venezuela). I have been working in research laboratories since 2016. In 2019, I joined The Immunopathology Laboratory of the Venezuelan Institute for Scientific Research (IVIC) as a research-associated professional, that is, a research assistant.

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