Osteopenia vs. Osteoporosis: Pathophysiology and Treatment Modalities
Overview
Osteopenia is a silent disease that develops in primarily seniors who may live healthy lifestyles, and have few risk factors. If left untreated osteopenia can progress into osteoporosis. This article addresses the pathophysiology and treatment modalities of osteoporosis.
Christine Johns DNP, MSN, MBA-NEA-BC, RN, PHN
Deirdre Jones MSN, MPH, RN, PHN, CIC
Meg Lyskawa MSN, RN, PHN
Osteopenia vs. Osteoporosis: Pathophysiology, Social determinants, and Treatment Modalities
Osteopenia is a silent disease that develops in primarily seniors who may live healthy lifestyles, and have few risk factors. Over 200,000 people worldwide are living with Osteoporosis, the later stage of Osteopenia. Osteopenia typically does not show symptoms until it becomes Osteoporosis. At that point, back pain caused by collapse of vertebrae, stooped posture, shortened height, and fractures from low impact indicate Osteoporosis has developed. A case study analyzing a postmenopausal woman with osteopenia was chosen out of interest in a common condition that seems to be a probability-based diagnosis for our team to consider as we grow older. The case presented shows that although one can live a healthy lifestyle, anyone can fall victim to osteopenia and the potential complications that can follow.
Social Determinants of Health and Epidemiology
There are social determinants of health that correlate to risk of developing osteopenia and osteoporosis, as well as access to the required scans and treatments can be limited as they are highly specialized. When affected patients have difficulty accessing DEXA scan locations, they can lack the treatment they need to improve their quality of life and lower their fracture risk. Socioeconomic Status (SES) in relation to current statistics of people living with osteopenia and osteoporosis in the United States is summarized as follows: Approximately 50% are female, 80-90% identify as white/European American, 23% identify as Hispanic, and approximately 10% identify as Black/African American, (Gough, Roberts, & Godde, 2023).
Pathophysiology of Osteopenia and Osteoporosis
Osteopenia refers to the early stages of bone loss, characterized by bone density that is below normal but not low enough to be classified as osteoporosis. This condition is typically asymptomatic and is often diagnosed through bone density tests (Reid et al, 2024). It is important to note that when Osteopenia is not treated it can develop into Osteoporosis. Osteoporosis is a more advanced stage of bone loss that significantly increases the risk of fractures. The primary mechanism behind osteoporosis is an imbalance in bone remodeling, where bone resorption by osteoclasts outpaces bone formation by osteoblasts (Föger-Samwald et al., 2020). This results in progressive bone disease, with structural integrity becoming compromised.
Bone remodeling involves a complex interplay of the endocrine, immune, and nervous systems. Genetic factors can also influence this process, and certain conditions such as menopause, being underweight, lack of exercise, and specific medications contribute to its progression. Osteoporosis is a multifactorial disease that often develops silently, progressively weakening bones without symptoms until a fracture occurs. Cortical bone, the dense outer layer, becomes thinner and more brittle, while trabecular bone, the spongy inner layer, loses density and structural connectivity (McCance & Huether, 2023).
Bone Resorption
Osteoporosis arises from increased bone resorption, which can be caused by estrogen deficiency and age-related factors. In postmenopausal women, decreased estrogen levels lead to heightened bone loss, as estrogen plays a critical role in preventing the secretion of RANKL (Receptor Activator of Nuclear Factor-kappa B Ligand) while promoting osteoclast-inhibiting fa ctors such as osteoprotegerin (OPG), GLP-1, and growth hormone (Liang et al., 2022). The reduction in these protective mechanisms accelerates bone resorption. Additionally, aging contributes to increased bone loss due to a natural decline in hormones like estrogen, testosterone, and growth hormone. This hormonal decline impairs the regulatory function of osteocytes, the cells responsible for overseeing bone remodeling, further exacerbating bone resorption and contributing to the development of osteoporosis (Liang et al., 2022).
Decreased Bone Formation
Decreased bone formation is a key contributor to osteoporosis, particularly as aging reduces the number and activity of osteoblasts, the cells responsible for bone formation. Aging also impairs the differentiation of mesenchymal stem cells into osteoblasts, further diminishing bone production. Additionally, osteocytes, the mechanosensing cells embedded within bone, become less responsive with age, reducing their ability to repair microdamage (Föger-Samwald et al., 2020). This results in an imbalance in bone remodeling, where the bone resorption phase surpasses the bone formation phase, leading to progressive thinning and increased fragility of the bones. Changes in bone structure also play a significant role in osteoporosis. The cortical bone, which forms the outer layer, becomes thinner and more porous, compromising its strength (Liang et al.,2022). Similarly, the trabecular bone, the spongy inner layer, loses density and connectivity, greatly reducing its ability to withstand mechanical stress (Liang et al., 2022). These structural changes exacerbate bone fragility.
Role of Cytokines and Hormones
Cytokines and hormones further regulate bone health through pathways such as the RANK/RANKL/OPG system. RANKL binds to RANK receptors on osteoclast precursors, promoting their maturation and increasing bone resorption (Föger-Samwald et al., 2020). OPG counteracts this by inhibiting RANKL binding, serving as a protective factor. Imbalances in this pathway that favor RANKL activity lead to excessive bone breakdown (Föger-Samwald et al., 2020). Other hormonal factors, such as chronically elevated parathyroid hormone (PTH) levels in primary hyperparathyroidism, also contribute to bone resorption. Additionally, vitamin D deficiency reduces calcium absorption, resulting in secondary hyperparathyroidism and further bone loss. These complex mechanisms collectively drive the progression of osteoporosis.
Risk Factors Contributing to Osteoporosis
Genetics: A family history of osteoporosis may predispose individuals to lower bone density.
Nutritional Deficiencies: Insufficient calcium and vitamin D intake reduces bone mineralization.
Chronic Diseases: Conditions such as rheumatoid arthritis, hyperthyroidism, and chronic corticosteroid use accelerate bone loss.
Postmenopausal estrogen loss.
Smoking.
Pharmacological Treatments
Alendronate, commonly known by the brand name Fosamax®, decreases the rate bone cells are absorbed. This reduced absorption allows the body to increase bone density, which in turn reduces the risk of fracture. Alendronate belongs to the class of bisphosphonate medications. On a molecular level, alendronate works binding to hydroxyapatite crystals within bone and then downregulates osteoclast-mediated bone resorption, thereby leading to a reduction in bone matrix breakdown. Both of these mechanisms collectively contribute to regulating the reabsorption and turnover of minerals. Alendronate differs from other bone-modifying supplements by its ability to suppress bone formation without modifying bone mineral accrual in endocortical or intracortical bone.
The bioavailability of alendronate is limited to 0.64% in fasting women and 0.59% in fasting men. However, this bioavailability diminishes by as much as 60% when the drug is taken with food.; hence why dosing instructions require the patient to take on an empty stomach. Alendronate exhibits a notably protracted terminal half-life of approximately 10 years within bone tissues. Alendronate is primarily excreted through urine, accounting for 50% of elimination, with unabsorbed drugs appearing in the feces (Wilkins P., Preuss C., 2024). The dosing recommendations are based on whether the patient’s goal is to treat or prevent osteoporosis.
Dosing
Osteoporosis treatment of Fosamax dosing is recommended to be: one 70 mg tablet once weekly - or - one bottle of 70 mg oral solution once weekly - or - one 10 mg tablet once daily. Osteoporosis prevention dosing is essentially half of the treatment dose: One 35 mg tablet once weekly or one 5 mg tablet once daily.
Calcium and Vitamin D
Calcium and vitamin D are essential nutrients for maintaining bone health and preventing osteoporosis. These nutrients complement each other. Calcium is a mineral that builds and maintains strong bones. The recommended daily intake for adults with osteoporosis: 1,200 mg. Sources of calcium include dairy products, leafy green vegetables, and fortified foods. Calcium supplements may be necessary for individuals who cannot meet their dietary needs. Vitamin D helps the body absorb calcium. The recommended daily intake for adults with osteoporosis: 800 IU. Sources of vitamin D include sunlight exposure, fatty fish, and fortified foods. Vitamin D supplements may be necessary for individuals with limited sun exposure or dietary intake.
Because Calcium and Vitamin D work in tandem, the benefits of having the recommended daily intake helps osteoporosis patients, reduce bone loss, lower the risk of fractures, improve bone mineral density, hence overall bone health.
In conclusion, calcium and vitamin D are crucial nutrients for preventing and managing osteoporosis. By consuming adequate amounts of these nutrients through diet or supplementation, individuals with osteoporosis can improve their bone health and reduce their risk of fractures.
Non-Steroidal Anti Inflammatories
While ibuprofen (Advil, Motrin) is a common pain reliever, it's not typically recommended for long-term use due to potential side effects such as stomach ulcers, kidney issues, and increased risk of cardiovascular problems (Rosen, H., 2024). Suggested alternatives like prescription NSAIDs like celecoxib (Celebrex), acetaminophen (Tylenol), or depending on the severity, even specific muscle relaxants or nerve pain medications (Rosen, H., 2024). According to researchers (Rosen, H., 2024) when NSAIDs are used regularly over an extended period of time, as is often the case with chronic pain, the potential for side effects increases. Evidence suggests that the potential for NSAID-associated complications increases as you get older.3 Some more common side effects include:
Stomach irritation and ulcers
Gastrointestinal (GI) bleeding
Increased potential for bruising
Exacerbation of asthma symptoms
Increased risk of stroke, heart attack, and blood clots
Kidney damage
The potential for NSAID complications may be increased for patients who:
Smoke
Drink alcohol regularly
Are a senior
Have a history of heart disease
Have high blood pressure
Have ever had any GI problems
Have kidney or liver disease
All NSAIDs, both prescription and over-the-counter, now sport warning labels thanks to a ruling by the Food and Drug Administration. Despite the warnings, using NSAIDs remains one of the most popular ways to relieve pain (Rosen, H., 2024).
Potential alternatives for long-term pain:
Prescription NSAIDs: Some prescription NSAIDs like celecoxib (Celebrex) may be considered safer for long-term use due to a lower risk of stomach irritation compared to other NSAIDs.
Acetaminophen (Tylenol): This is often considered a safer option for long-term pain relief compared to most NSAIDs, but can still have side effects if taken in high doses.
Topical pain relievers: Creams or gels containing capsaicin can be helpful for localized pain.
Muscle relaxants: Depending on the source of pain, muscle relaxants may be prescribed.
Nerve pain medications: If the pain is related to nerve damage, specific medications like gabapentin or pregabalin may be prescribed.
Non - Pharmacological Treatment
Alongside medication, consider non-pharmacological pain management strategies like exercise, physical therapy, stress management, and weight management. Nonpharmacological therapies for osteoporosis emphasize lifestyle changes, dietary improvements, and physical activity to maintain bone health, prevent fractures, and enhance quality of life. Nutritional interventions are critical, including adequate calcium and vitamin D intake from sources like dairy products, leafy greens, fortified foods, and sunlight. A balanced diet rich in fruits, vegetables, lean protein, and whole grains supports overall bone health, while excessive salt, caffeine, and alcohol should be limited. Other nutrients, such as magnesium and phosphorus from nuts, seeds, legumes, and whole grains, also play essential roles in bone mineralization.
Physical activity is a cornerstone of osteoporosis management, with weight-bearing exercises like walking, dancing, and jogging stimulating bone formation. Resistance training strengthens muscles and enhances bone density, while balance and flexibility exercises, such as yoga and Tai Chi, reduce fall risks by improving stability. Lifestyle modifications further contribute to bone health; quitting smoking and limiting alcohol intake help minimize bone loss. Fall prevention measures, including using supportive footwear, removing tripping hazards, and installing grab bars at home, are also vital to reducing fracture risks.
Physical therapy can play a role by offering postural training to strengthen core muscles and customized exercise programs tailored to an individual’s needs. Mind-body approaches, such as mindfulness meditation and stress management, indirectly support bone health by mitigating stress-related hormonal changes that could impact bone density. Sunlight exposure is another critical component, as it helps maintain adequate vitamin D levels necessary for calcium absorption and bone strength. Assistive devices like orthopedic braces or supports may provide additional stabilization for fractures or weak bones.
Regular bone density monitoring using tools such as DEXA scans is essential to evaluate bone health and guide both non pharmacological and pharmacological interventions. Together, these strategies form a comprehensive approach to preventing and managing osteoporosis, reducing fracture risks, and improving overall well-being. Consultation with healthcare providers, including dietitians, physical therapists, and doctors, ensures an individualized plan tailored to specific needs and goals.
Epidemiology
The World Health Organization (WHO) estimates that osteoporosis affects 200 million women worldwide (International Osteoporosis Foundation, n.d.).
According to the WHO criteria, “30% of postmenopausal women have Osteoporosis and 54% have Osteopenia” (Bellantoni, , n.d., para. 2). Osteoporosis is a “ major non-communicable disease and the most common bone disease, affecting one in three women and one in five men over the age of 50 worldwide” (International Osteoporosis Foundation, n.d). Worldwide in 2019, fractures accounted for 25.8 million years lived with disability (YLDs), an increase of 65.3% of the absolute YLDs since 1990. The prevalence of Osteopenia among males and females of all age groups is roughly 40.5% and 7.93% for Osteoporosis. For adults over age 50, Osteopenia is at a 42.3% rate and Osteoporosis at a 8.96% prevalence which accounts for the majority, (Fan, et. al, 2024).
Physical assessment
A Dexa (dual x-ray absorptiometry) scan post-exam is recommended for identifying potential for fractures and assessing overall bone density. This is conducted by “passing a high and low energy XRay beam through the body…[to] diagnose specific conditions such as bone thinning” (CDC, 2024). The CDC also teaches that the amount of radiation is very low and is generally considered for women aged 65 and older, or for women between ages 50-64 if they have certain risk factors, such as family history.
Upon physical examination of each limb and joint, the patient will be instructed to provide feedback on pain, stiffness, spasms, and instability. Range of motion (ROM) will be measured using a goniometer, which assists in calculating the angular degrees of motion for abnormal findings (increased or decreased ROM). In an example case where a postmenopausal patient reports having experienced a hyperextension of one of her lower legs and has limited range of motion as a result with a history of bilateral knee tendonitis would primarily be examined with passive ROM assessments on the injured leg, as recommended by Ball, et. al (2023). Given the state of her knee and lower leg injury, the following addresses the method of examination.
While the patient is supine, the practitioner would ask the patient to flex the non-injured knee up to 130 degrees (using a goniometer) and extend it up to 15 degrees - keeping in ming that she had tendonitis in both knees.
Documentation would likely show:
Active ROM: Non-injured left knee flexion: 90 degrees, Extension: 10 degrees. Pain level 2/10.
Passive ROM: Non-injured left knee flexion: 130 degrees, Extension: 10 degrees. Pain level 2/10.
Following this process, the same would be assessed on the injured leg.
Documentation would likely show:
Active ROM: Injured right knee flexion: 10 degrees, Extension: 0 degrees. Pain level 6/10.
Passive ROM: Injured right knee flexion: 45 degrees, Extension: 0 degrees. Pain level 6/10.
Upon examination and palpation, tenderness at a localized, specific point on the body (also known as point tenderness) is a likely identifier of a location that has sustained a fracture and may be accompanied by slight deformities (Campagne, 2024). Pertinent positives include deformity, severe pain, swelling, decreased or no mobility, bruising, and crepitus, confirmed with the appropriate radiographic scans. Negative indicators would be mobility intact, no swelling, and unremarkable XRay and may instead suggest a sprain or non-fracture skeletal injury.
The main difference between a skeletal injury and a muscular injury lies in the structures involved. A skeletal injury refers to damage to the bones, such as a fracture and a muscular injury affects the muscles, tendons, ligaments, or other soft tissues of the musculoskeletal system (Fernades et al., 2015). If a patient reports hyperextension of the
knee, it would be safe to suspect ligament, tendon, or soft tissue damage around the patellar and lower leg with consideration of possible fracture around the tibial head. This could be ruled out with imaging to see if there is damage to the proximal tibiofibular joint. One aspect to note is the healing for a muscular injury involves repair process and a bone injury involves a regeneration of bone tissue (Fernades et al., 2015).
The treatment of osteoporosis aims to reduce the risk of fractures, enhance bone strength, and improve overall quality of life. By combining medications, lifestyle changes, and preventive measures, patients can effectively manage the condition and maintain independence. Regular monitoring and close collaboration with healthcare professionals are essential to ensure optimal treatment outcomes. Early intervention and consistent adherence to the treatment plan are key to preserving bone health and preventing complications.
References
Ball, J., Dains, J., Flynn, J., Solomon, B., & Stewart, R. (2023). Seidel’s Guide to Physical Examination: an Interprofessional Approach.
Bellantoni, M. F. (n.d.). Osteoporosis information. Johns Hopkins Arthritis Center. Retrieved from https://www.hopkinsarthritis.org/arthritis-info/osteoporosis-info/
Campagne, D. (2024). Overview of Fractures. MERCK Manuals, Professional Version. Retrieved from
https://www.merckmanuals.com/professional/injuries-poisoning/fractures/overview-of-fractures
CDC. (2024). Facts about Bone Density (DEXA Scan). Retrieved from: https://www.cdc.gov/radiation-health/data-research/facts-stats/dexa-scan.html
Fan, Y., Li, Q., Liu, Y., Miao, J., Zhao, T., Cai, J., Liu, M., Cao, J., Xu, H., Wei, L., Li, M., & Shen, C. (2024). Sex- and Age-Specific Prevalence of Osteopenia and Osteoporosis: Sampling Survey. JMIR public health and surveillance, 10, e48947. https://doi.org/10.2196/48947
Fernandes, T. L., Pedrinelli, A., & Hernandez, A. J. (2015). MUSCLE INJURY - PHYSIOPATHOLOGY, DIAGNOSIS, TREATMENT AND CLINICAL PRESENTATION. Revista brasileira de ortopedia, 46(3), 247–255. https://doi.org/10.1016/S2255-4971(15)30190-7
Föger-Samwald, U., Dovjak, P., Azizi-Semrad, U., Kerschan-Schindl, K., & Pietschmann, P. (2020). Osteoporosis: Pathophysiology and therapeutic options. EXCLI journal, 19, 1017–1037. https://doi.org/10.17179/excli2020-2591
Gough Courtney, M., Roberts, J., & Godde, K. (2023). Structural Inequity and Socioeconomic Status Link to Osteoporosis Diagnosis in a Population-Based Cohort of Middle-Older-Age Americans. Inquiry : a journal of medical care organization, provision and financing, 60, 469580231155719. https://doi.org/10.1177/00469580231155719
Harvard Health. (2021). Osteopenia:When you have weak bones, but not osteoporosis. https://www.health.harvard.edu/womens-health/osteopenia-when-you-have-weak-bones-but-not-osteoporosis
Hou, X., Tian, F. (2023). STAT3 hints at therapeutic targets for treating osteoporosis, 15 April 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-2818836/v1]
International Osteoporosis Foundation. (n.d.). Epidemiology. Retrieved from https://www.osteoporosis.foundation/health-professionals/about-osteoporosis/epidemiology#:~:text=Worldwide%2C%20osteoporosis%20is%20estimated%20to,WHO%20Scientific%20Group%20Technical%20Report.
Katz, J. N., Arant, K. R., & Loeser, R. F. (2021). Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA, 325(6), 568–578. https://doi.org/10.1001/jama.2020.22171
Liang, B., Burley, G., Lin, S. et al. Osteoporosis pathogenesis and treatment: existing and emerging avenues. Cell Mol Biol Lett 27, 72 (2022). https://doi.org/10.1186/s11658-022-00371-3
McCance, K. L., & Huether, S. E. (2023). Pathophysiology: The Biologic Basis for Disease in Adults and
Children (9th ed.). Elsevier, St. Louis, MO.
Reid, I. R., & colleagues. (2024). Osteopenia: A key target for fracture prevention. The Lancet
Diabetes & Endocrinology, 12(11), 856–864. https://doi.org/10.1016/S2213-8587(24)00211-8
Rosen, H., 2024. Calcium and Vitamin D Supplementation in Osteoporosis.
https://www.uptodate.com/contents/calcium-and-vitamin-d-supplementation-in-osteoporosis.
Ward, K. A., Pearse, C. M., Madanhire, T., Wade, A. N., Fabian, J., Micklesfield, L. K., & Gregson, C. L. (2023). Disparities in the Prevalence of Osteoporosis and Osteopenia in Men and Women Living in Sub-Saharan Africa, the UK, and the USA. Current osteoporosis reports, 21(4), 360–371. https://doi.org/10.1007/s11914-023-00801-x
Wilkins Parker LR, Preuss CV. Alendronate. [Updated 2023 Nov 12]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
Available from: https://www.ncbi.nlm.nih.gov/books/NBK526073/