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Bones Composition and Remodelling

Bones are living tissues that are broken down constantly and replaced. They have evolved to be strong yet light. The long bines have a stringy outer shell that surrounds a spongier core termed "trabecular bone." This combination helps in making the bone light and strong. Bones can grow, heal, and respond to the environment, and bone remodelling is an important process (Tu et al., 2020). Daily remodelling is gradual mineral resorption on the inside of the bone cavity and the cortical layer, leading to a widening of the bone cavity and a loss of trabecular bone which is compensated for through the addition of extra mineral layers gradually to the outer part of the cortical layer (Akkawi & Zmerly, 2018).  In normal humans, osteoblastic activity occurs that includes osteoblast cells that help to develop bones. The mass of the bone is maintained by balancing the osteoblasts that form the bone and the other cells like the osteoclasts that remove the bone. This bond helps in achieving homeostasis in the bone, but it gets compromised when a person suffers from osteoporosis.

In this paper, a discussion will be held regarding the pathophysiology, osteoporosis mechanism, and the application of bisphosphonates. The paper further discusses the application of nursing knowledge related to this disorder and the medications for improving the patient’s overall health. The importance of patient education and nursing consideration about this drug will be discussed. The paper focuses on osteoporosis and the application of bisphosphonates for improving patient outcomes.

In the human body, the balance among bone deposition and bone reabsorption is determined through the activity of osteoclasts and osteoblasts. In the bone remodelling cycle, osteoclasts get activated, causing bone absorption and, after a brief phase of reversal, the resorption pit gets occupied by the precursors of osteoblasts (Akkawi & Zmerly, 2018).   Formation of bone beads as progressive waves of osteoblasts form as they lay down the fresh bone matrix. An increase in remodelling activity, for example, can result in bone loss. Prostaglandins stimulate formation and bone resorption, and the first step of prostaglandin formation is initiated through the enzyme cyclooxygenase 2 (COX2), and inhibitors of COX2 can inhibit the formation of bone in animals in response to mechanical stress. The lipoprotein (LDL)-related protein 5 receptor is present on the surface of osteoblast precursor cells. Sclerostin is a protein produced by the SOST gene as well as expressed by the osteocytes that bind to the LRP5 receptor, inhibiting the Wnt signalling that causes a reduction in bone formation (Akkawi & Zmerly, 2018). Osteoporosis is thus a metabolic bone disease that occurs when the osteoclastic bone resorption is not compensated for through osteoblastic bone formation, resulting in weakness and fragility of the bones, and a person becomes at high risk of developing fractures (Samwald et al., 2020).

One pharmacological treatment in response to osteoporosis is the administration of bisphosphonates. Risedronate is a pyridine-based bisphosphonate that is sold under the brand name Actonel®. Its chemical name is sodium; hydroxy-(1-hydroxy-1-phosphono-2-pyridin-3-ylethyl) phosphinate (McClung & Ebetino, 2020). Risedronate belongs to a class of medication called bisphosphonates which helps prevent the breakdown of the bone as well as increase the density and thickness of the bone (Hameed, 2018).

Mechanism of Osteoporosis

The mechanism of action includes Risedronate acid that binding to bone hydroxyapatite. Bone resorption leads to local acidification and thus releases Risedronic acid, that is taken into osteoclasts through endocytosis1. Endocytic vesicles get acidified and release Risedronic acid into the osteoclast’s cytosol, inducing apoptosis through the inhibition of farnesyl pyrophosphate synthase. Thus, inhibition of osteoclasts causes a reduction in bone resorption and helps in treating osteoporosis (McClung & Ebetino, 2020).

This drug is indicated for treating osteoporosis in men, Paget’s disease, preventing and treating osteoporosis in postmenopausal women, and preventing glucocorticoid-induced osteoporosis (McClung & Ebetino, 2020).

For orally administered Risedronate, the absolute bioavailability is approximately 0.6%, which is independent of its formulation (Cardozo, Karatza & Karalis, 2021). Variability in pharmacokinetics is associated with variability in absorption following drug admission orally. Patients who are suffering from the inflammatory oesophagus, stomach ulcers, low levels of calcium in the blood, achalasia of the oesophageal lining, inflammation surrounding the tissue of the tooth, etc. must not take this drug (Lima et al., 2019). The precautions include that the medicine must not be split, crushed, or chewed as this will affect its composition and bioavailability (Thomasius et al., 2020).Sucking or holding it in the mouth is prohibited. After taking this medication, it is important to not drink or eat anything or take any other medications for about 30 minutes. Furthermore, one should not lie down after administering this drug for about 30 minutes. The side effects of this drug include joint pain, nausea, indigestion, headache, diarrhoea, constipation, etc. 

It is also important to understand the drug interaction for Risedronate. Risedronate can increase the risk of gastrointestinal bleeding when Aceclofenac, Acemetacin, or acetylsalicylic acid is taken along with Risedronate. People who are overweight are at a high risk of developing hypercholesterolemia. This can be a problem because certain medications used to treat hypercholesterolemia, such as Acipimox, can worsen myopathy, myoglobinuria, and rhabdomyolysis when combined with Risedronate. The risk of hypocalcaemia and nephrotoxicity can be increased if acyclovir is combined with Risedronate. Medications like Quinapril, Sucralfate, Didanosine, and Bismuth Subsalicylate might interfere with the absorption of Risedronate, and hence these products must be administered with a minimum gap of 30 minutes after taking Risedronate (Thomasius et al., 2022). 

Patients who have issues with swallowing, digestive problems, or low calcium levels in their blood must not take this medication. Along with timely administration of the drug, it is also important to follow certain guidelines such as maintaining a healthy diet rich in calcium and vitamin D content, engaging in exercise, reducing the consumption of alcohol, caffeine, smoking, and so on. It is also important to avoid multivalent ions such as calcium, divalent ions and antacids that interfere with medicine absorption (Peng et al., 2020).This medication must be stopped temporarily after three to five years and is also called a "bisphosphonate holiday." People with severe osteoporosis, on the other hand, may need to wait up to ten years before discontinuing this medication.

Knowledge about osteoporosis and the treatment drug can help in reducing the risk of the occurrence of adverse situations. For example, educating the patient about osteoporosis and the factors that might progress this issue can help in reducing the risk of an adverse situation. Furthermore, educating the patient about the complications of osteoporosis, such as pain, limited mobility, ricks of fracture, and so on, can help with therapeutic adherence (Cornelissen et al., 2020). Furthermore, as a nurse, learning about medications and drug interactions can help to reduce the likelihood of a serious situation. For example, if the patient is suffering from hypercholesterolemia and is prescribed Acipimox, which is a lipid-lowering drug, taking Acipimox and Risedronate together can increase the risk of myopathy, myoglobinuria, and rhabdomyolysis (Cardozo, Karatza & Karalis, 2021).  Thus, taking both medications at an interval of 30 minutes can help eliminate these issues. Further assessing the knowledge of the patient related to osteoporosis and educating them about dietary exercises like increasing the intake of vitamin D and calcium, identifying foods with high calcium levels, and limiting the consumption of beverages that are high in phosphorus (Cornelissen et al., 2020). Furthermore, educating the patient about regular screening like the bone density test and making healthy life choices like cessation of smoking or alcohol is important (Patel et al., 2018).

Pharmacological Treatment with Bisphosphonates

 Furthermore, providing emotional support to the patient, showing empathy and compassion, and involving friends and family can be effective approaches to facilitate the rate of recovery. Also, respecting the values, preferences, and dignity of the patient can help to develop therapeutic relationships that can help the patient express their needs, leading to patient satisfaction (Nayak & Greenspan, 2018).  Furthermore, educating the patient about the side effects and the severe side effects can help in consulting a physician when an adverse condition arises and, as a result, prompt action can be taken accordingly. Providing this information to the patient can help the patient stick to their diet plan, increase therapeutic adherence, and reduce the risk of progression of osteoporosis (Nayak & Greenspan, 2018).  

Conclusion

Thus, osteoporosis causes brittleness and weakness in the bones, and as a result, a fall or bending over might cause a fracture. Medication like Risedronate or bisphosphonates can be an effective treatment for osteoporosis and prevent the progression of this disease. However, it is important that while administering the drug, a person should know its side effects, drug interactions, etc. Following a diet plan that is rich in vitamin D and calcium can help facilitate the rate of recovery. Apart from bisphosphonates. The alternative treatment includes Denosumab, hormone-related therapy, or bone-building medications like Teriparatide. Apart from treatment, it is also important to educate the patient about the complications associated with osteoporosis to improve therapeutic adherence. Mild exercise and adhering to a proper diet plan can both contribute to healthy outcomes. Emotional support and care can help in facilitating the process of recovery.

References

Akkawi, I., & Zmerly, H. (2018). Osteoporosis: current concepts. Joints, 6(02), 122-127. https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0038-1660790

Cardozo, B., Karatza, E., & Karalis, V. (2021). Osteoporosis treatment with risedronate: a population pharmacokinetic model for the description of its absorption and low plasma levels. Osteoporosis International, 32(11), 2313-2321. https://link.springer.com/article/10.1007/s00198-021-05944-0

Cornelissen, D., de Kunder, S., Si, L., Reginster, J. Y., Evers, S., Boonen, A., & Hiligsmann, M. (2020). Interventions to improve adherence to anti-osteoporosis medications: an updated systematic review. Osteoporosis International, 31(9), 1645-1669. https://link.springer.com/article/10.1007/s00198-020-05378-0

Hameed, B. H. (2018). Risedronate as a therapeutic trial post-hysterectomy in premenopausal women to prevent osteoporosis. Al-Kindy College Medical Journal, 14(1), 4-7. https://jkmc.uobaghdad.edu.iq/index.php/MEDICAL/article/view/6

Lima, T. B., Santos, L. A. A., Nunes, H. R. D. C., Silva, G. F., Caramori, C. A., Qi, X., & Romeiro, F. G. (2019). Safety and efficacy of risedronate for patients with esophageal varices and liver cirrhosis: a non-randomized clinical trial. Scientific reports, 9(1), 1-9. https://www.nature.com/articles/s41598-019-55603-y

McClung, M. R., & Ebetino, F. H. (2020). History of risedronate. Bone, 137, 115407. https://www.sciencedirect.com/science/article/pii/S8756328220301873

Nayak, S., & Greenspan, S. L. (2018). How can we improve osteoporosis care? A systematic review and meta?analysis of the efficacy of quality improvement strategies for osteoporosis. Journal of Bone and Mineral Research, 33(9), 1585-1594. https://asbmr.onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3437

Patel, D., Worley, J. R., Volgas, D. A., & Crist, B. D. (2018). The effectiveness of osteoporosis screening and treatment in the Midwest. Geriatric Orthopaedic Surgery & Rehabilitation, 9, 2151459318765844. https://journals.sagepub.com/doi/abs/10.1177/2151459318765844

Peng, L., Reynolds, N., He, A., Liu, M., Yang, J., She, P., & Zhang, Y. (2020). Osteoporosis knowledge and related factors among orthopedic nurses in Hunan province of China. International journal of orthopaedic and trauma nursing, 36, 100714. https://www.sciencedirect.com/science/article/pii/S1878124119300036

Samwald, U., Dovjak, P., Azizi-Semrad, U., Kerschan-Schindl, K., & Pietschmann, P. (2020). Osteoporosis: pathophysiology and therapeutic options. EXCLI journal, 19, 1017. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7415937/

Thomasius, F., Palacios, S., Alam, A., Boolell, M., Vekeman, F., & Gauthier, G. (2022). Fracture rates and economic outcomes in patients with osteoporosis prescribed risedronate gastro-resistant versus other oral bisphosphonates: a claims data analysis. Osteoporosis International, 33(1), 217-228. https://link.springer.com/article/10.1007/s00198-021-06108-w

Tu, K. N., Lie, J. D., Wan, C. K. V., Cameron, M., Austel, A. G., Nguyen, J. K., ... & Hyun, D. (2018). Osteoporosis: a review of treatment options. Pharmacy and Therapeutics, 43(2), 92. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768298/

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