|Year : 2022 | Volume
| Issue : 1 | Page : 1-7
Osteoporosis: A narrative review of diagnosis and treatment
Dheeraj, Nirmal Kumar, Kavya Ronanki, Ravi Kant
Department of General Medicine, AIIMS, Rishikesh, Uttarakhand, India
|Date of Submission||27-Jan-2022|
|Date of Decision||31-Mar-2022|
|Date of Acceptance||19-Apr-2022|
|Date of Web Publication||23-Jan-2023|
Department of General Medicine, AIIMS, Rishikesh, Uttarakhand
Source of Support: None, Conflict of Interest: None
Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue, with a subsequent increment in bone fragility and susceptibility to fracture. It is the most common metabolic bone disorder. It is a common condition affecting one in three women and one in five men over 50, resulting in substantial morbidity, excess mortality, and health and social services expenditure. Osteoporosis is undertreated and underrecognized, considering the silent nature of the disease. Therefore, it is essential to develop strategies for early detection, prompt prevention, and treatment of osteoporosis in both men and women. This paper reviews the risk factors associated with osteoporosis, diagnostic approach, investigation, and management. This should include multidynamic lifestyle changes to reduce bone loss and decrease the risk of falls and identify and treat secondary causes of bone loss and specific treatment for osteoporosis. Hormone replacement therapy, raloxifene, bisphosphonates, calcium and Vitamin D, calcitonin, and parathyroid hormone have all been shown to improve bone density and decrease the risk of fracture in specific situations. Treatment must be tailored to the individual patient to ensure compliance and optimize the potential benefits.
Keywords: Bone mineral density, metabolic bone diseases, osteoporosis
|How to cite this article:|
Dheeraj, Kumar N, Ronanki K, Kant R. Osteoporosis: A narrative review of diagnosis and treatment. J Uttaranchal Orthop Assoc 2022;1:1-7
|How to cite this URL:|
Dheeraj, Kumar N, Ronanki K, Kant R. Osteoporosis: A narrative review of diagnosis and treatment. J Uttaranchal Orthop Assoc [serial online] 2022 [cited 2023 Jun 3];1:1-7. Available from: http://www.juoa.org/text.asp?2022/1/1/1/368384
| Introduction|| |
Osteoporosis is a skeletal disease defined by low bone mass and microarchitectural deterioration of bone tissue, with a subsequent increase in bone fragility and susceptibility to fracture. According to the International Osteoporosis Foundation, it is estimated that worldwide, one in three women and one in five men over the age of 50 will experience osteoporosis fractures in their remaining lifetimes. They also highlighted that in 2006, osteoporosis caused more than 8.9 million fractures annually, resulting in an osteoporosis fracture every 3 seconds. A meta-analysis of 86 studies with a sample size of 103,334,579 people in the age range of 15–105 years showed the prevalence of osteoporosis in the world to be 18.3%, among women to be 23.1%, and among men to be 11.7%.
While data on the prevalence of osteoporosis in India are limited, estimates suggest that of the 230 million Indians expected to be over the age of 50 years in 2015, 20% are osteoporotic women. Modagan et al., in their study, revealed that the prevalence of osteoporosis and osteopenia was 24.7% and 44.6% among the South Indian study population in the age group between 30 and 90 years, respectively. Marwaha et al. showed that the prevalence of osteoporosis was 35.1% among 1600 healthy controls more than 50 years of age residing in Delhi, India.
Osteoporosis is not clinically evident until a fracture occurs. Fractures cause increased mortality and disability and increase medical costs. Studies have shown that in U. S. women 55 years and older, the hospitalization burden of osteoporotic fractures and population facility-related hospital costs is more significant than MI, stroke, or breast cancer.
The National Institutes of Health Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy defines osteoporosis as a skeletal disorder characterized by compromised bone strength, predisposing a person to increased fracture risk. Bone strength principally reflects the integration of bone density and bone quality. Although this definition covers all components of osteoporosis, estimation of bone mineral mass and microarchitectural structure has been a complex phenomenon. As far as an enormous number of papers have been produced on this matter, we aimed to create an easy and practical narrative review for the colleagues looking for a summary on osteoporosis, particularly for those approaching it for the first time.
| Methods|| |
We searched PubMed, Embase, and the Cochrane Database using the following search terms: “osteoporosis” or “metabolic bone disease” and “diagnosis” or “treatment.” Studies were included in the review if they were randomized controlled trials, review, or guidelines; limits: English and human adults.
| Discussion|| |
Risk factors for osteoporosis
Risk factors contributing to osteoporosis can be broadly classified as nonmodifiable and modifiable risk factors.
Nonmodifiable risk factors comprise sex, age, race, and ethnicity. The Framingham Osteoporosis Study evaluated the bone mineral density (BMD) at the hip, lumbar spine, and the radius in 800 elderly men and women with a mean age of 74 years. They showed that the average 4-year bone loss at all sites was 0.2%–3.6% for men compared with 3.4%–4.8% for women. Studies have shown that women aged 50 years or older have a four times elevated rate of osteoporosis and a two times higher rate of osteopenia than men. The annual incidence of fragility fractures increases with age, and nonvertebral and hip fractures are more common in older age. Compared to non-Asian women, Asian Indian women have a 5%–15% lower BMD.
Modifiable risk factors include nutritional status, nutritional factors, lifestyle, and drugs. Low body mass index (BMI) is a well-documented risk factor for future fracture. Hariri et al., in their study, have shown that diabetic patients with high BMI possibly have a low risk of developing osteoporosis than those with low BMI, and low BMI (<18.5 kg/m2) could be a risk factor for osteoporosis. Nutritional factors, chiefly calcium and Vitamin D, play a significant role in influencing the risk of osteoporosis. Studies have reported that Indian diets do not meet the recommended dietary allowances recommended by the Indian Council of Medical Research and highlighted the dual deficiency of calcium and Vitamin D. A sedentary lifestyle, decreased exposure to sunlight, low physical activity, and lack of exercise are all associated with lower BMD. Exposure to oral glucocorticoids for more than 3 months at a dose of prednisolone of 5mg daily or more and daily consumption of alcohol 3 or more units are also the risk factors for developing osteoporosis.
Secondary causes of osteoporosis include rheumatoid arthritis, untreated hypogonadism, inflammatory bowel disease, prolonged immobility, organ transplantation, type 1 diabetes, thyroid disorders, and chronic obstructive pulmonary disease.
The fracture risk assessment tool (FRAX) is a great aid to assess a patient's risk factors for fracture. The FRAX is extensively used in estimating the 10-year probability of hip fracture and the 10-year probability of a major osteoporotic fracture (clinical spine, forearm, hip, or shoulder fracture). The FRAX tool factors include hip BMD, age, gender, height, weight, family history of hip fracture, smoking, steroid use >3 months, rheumatoid arthritis, and alcohol use. The FRAX algorithm is country specific and designed to use previously untreated postmenopausal women and men aged 40–90 years. The National Osteoporosis Foundation (NOF) recommends treatment in patients with a 10-year probability of a hip fracture >3% or a 10-year probability of a major osteoporosis-related fracture more than or equal to 20% based on FRAX.
Diagnosis of osteoporosis
The NOF recommends that BMD testing is performed in all women ≥65 years and men ≥70 years. The U. S. Preventive Services Task Force (USOSTF) recommends screening all women ≥65 years and younger women whose fracture risk is the same or greater than that of a 65-year-old woman who has no additional risk factors. The Indian Society for Bone and Mineral Research (ISBMR) has recommended screening at an earlier age. The ISBMR recommends screening of:
- Women aged 60 and older and men aged 65 and older, regardless of clinical risk factors
- Postmenopausal women younger than 60 years and men aged 50–64 years when there are concerns for osteoporosis based on their clinical risk factor profile
- Women in the menopausal transition if there is a specific risk factor associated with increased fracture risk, such as low body weight, prior low-trauma fracture, or high-risk medication
- Individuals who have had a fragility fracture before the age of 50 years
- Individuals with a condition (e.g., rheumatoid arthritis, diabetes mellitus, and malabsorption syndrome) or who are taking medication (e.g., glucocorticoids in a daily dose ≥5 mg prednisone or equivalent for ≥3 months) associated with low bone mass or bone loss
- Any individual being considered for pharmacologic therapy for osteoporosis.
Multiple methods have been used to assess both bone quality and bone quantity, including BMD, trabecular bone score (TBS), quantitative computed tomography (QCT), bone histomorphometry, microindentation, and bone turnover markers. BMD measured by dual-energy X-ray absorptiometry (DXA) is currently the gold standard for both osteoporosis diagnosis and the monitoring of treatment efficacy. The gold standard technique for estimating BMD is the dual-energy X-ray absorptiometry (DXA) technique because of its reproducibility, extensive normative data, noninvasive nature, the little time required for the procedure, and minimal radiation exposure. In 1994, World Health Organization gave the operational definition of osteoporosis based on bone mineral density and classified it as normal: BMD within 1 SD of a young-adult reference population; osteopenia, or low bone mass: BMD between 1 and 2.5 SD below that of a young-adult reference population; osteoporosis: BMD 2.5 SD or more below that of a young-adult reference population.
Dual-energy X-ray absorptiometry (DXA) is a projectional X-ray-based technology demonstrated to precisely and accurately measure BMD at specific sites: the lumbar spine, hip, and distal forearm. Two X-ray beams at distinct energy levels are used to subtract the patient's soft-tissue absorption, providing a measurement of skeletal BMD. The effective radiation dose for both lumbar spine and hip scanning is relatively equivalent to a chest X-ray.
QCT produces a volumetric BMD, in opposition to the areal BMD of the DXA, which is established on a two-dimensional projectional area measurement. QCT can be performed on most commercially available computed tomography scanners, provided they include densitometry analysis software and a calibration phantom. One significant distinction in technologies relates to monitoring spine BMD values measured by QCT demonstrate relatively increased rates of bone loss with advanced age compared with DXA values because of the exclusively cancellous bone measurements of QCT: the rate of change in cancellous bone is higher than that of cortical bone.
TBS is derived from the texture of the spine dual X-ray absorptiometry (DXA) image. It is relevant to bone microarchitecture and fracture risk, providing information independent of BMD.
Various other imaging-based diagnostic techniques are being developed for bone assessment. Vertebral fracture assessment is a DXA diagnostic technology that allows imaging of the thoracic and lumbar spine to search for the presence of vertebral fractures. It is a convenient and reliable low-cost and low-radiation method. VFA is indicated when the T-score <−1 and one or more of the following are present: a woman of 70 years or older, a decrease of more than 4 cm in height, a self-reported but not documented vertebral fracture, and corticosteroid therapy in doses equivalent to prednisone 5 mg or more per day for 3 or more months. Radiofrequency Echographic Multi Spectrometry is an ultrasound technique based on analyzing unfiltered ultrasound raw signals obtained during an ultrasound scan of the lumbar spine and/or the femoral neck, whose result is reported as the ultrasonographic BMD expressed in g/cm2. Fragility score is an ultrasound parameter that estimates skeletal fragility based on a transabdominal ultrasound scan of the lumbar vertebrae. It has shown a good correlation with the fracture risk estimated by the FRAX score.
Microindentation is a technique that can directly assess the mechanical characteristics of cortical bone in vivo. Although the invasive procedure restricts its wide use as a clinical tool, microindentation helps shed light on bone quality change. Bone histomorphometric analysis of bone biopsies directly approaches bone remodeling rates at the tissue level. Newer modalities measuring bone turnover markers are being studied. In patients with osteoporosis, the levels of multiple bone turnover markers are altered. Studies have shown that osteocalcin and C-terminal telopeptide of type 1 collagen are significantly lower in people with osteoporosis.
Evaluation of the osteoporotic patient
An appropriate medical, clinical, and laboratory evaluation is indicated in all adults diagnosed with osteoporosis who have an osteoporotic fracture history or are identified as a high risk given to coexisting medical conditions that contribute to bone loss. In addition, laboratory tests should be completed to exclude secondary causes of bone loss, which are often treatable.
The prevalence of secondary causes of Osteoporosis (O. P.) is high in adults. Up to 30% of postmenopausal women and 50% of men with O. P. may have an underlying cause. Secondary causes for O. P. should be suspected in patients with a fragility fracture despite having no risk factors for O. P. In patients with osteoporosis, a basic biochemical and hormonal profile, including serum calcium, phosphorous, and intact parathyroid hormone, should be done.
Treatment of osteoporosis
Management of osteoporosis includes treating an acute fracture, underlying disease, risk factor reduction, nutrition, exercise, and pharmacological treatment of osteoporosis.
Treatment of acute fracture
Depending on the severity of the fracture, a surgical procedure may include open reduction, internal fixation, hemiarthroplasties, and total arthroplasties. Vertebral compression fractures sometimes present suddenly with sudden-onset backache. Vertebral, rib, and pelvic fractures are managed conservatively. Analgesics are given for pain, muscle relaxants for muscle spasms, and early mobilization should be done to prevent further bone loss.
Adequate calcium intake should be ensured for both osteoporosis prevention and treatment, as shown in [Table 1]. For adults aged 50 years or more, the recommended calcium intake is 1200 mg/day.Vitamin D is essential for calcium absorption and bone health and also helps in improving muscle performance, the balance that reduces the risk of falling. Optimal Vitamin D intake increases response to bisphosphonates. It has been recommended to maintain a daily intake of at least 1000 IU of Vitamin D per day for adults aged 50 years or more.
Pharmacological treatment should be considered in those having: a. T-score below 2.5, b. having osteoporosis-related fracture, c. postmenopausal women with a fracture and d. having multiple risk factors even if BMD is not in the osteoporotic range.
Pharmacological therapies used can be either antiresorptive or anabolic. Antiresorptive medications decrease the rate of bone resorption, whereas anabolic medications increase bone formation more than bone resorption. Antiresorptive therapies include estrogen analogs, SERMS, bisphosphonates, denosumab, and calcitonin. The only approved anabolic agent is teriparatide. [Table 2] shows the Food and Drug Administration (FDA) list of drugs to treat and prevent osteoporosis.
|Table 2: Drugs approved by FDA for treatment and prevention of osteoporosis|
Click here to view
Estrogens analogs reduce bone turnover, prevent bone loss, and induce a slight increase in bone mass in the spine, hip, and total body. They can be given orally and transdermally. The FDA approves estrogen for the prevention of postmenopausal osteoporosis. They should only be considered for women at significant risk of osteoporosis when nonestrogen agents cannot be used. Estrogen should be combined with progestin to protect against endometrial stimulation. Conjugated equine estrogen, with or without medroxyprogesterone acetate, reduced fractures at spine, hip, and nonvertebral sites in postmenopausal women.
Raloxifene is approved to prevent and treat postmenopausal osteoporosis and reduce the risk of breast cancer in women with postmenopausal osteoporosis or at high risk of breast cancer. Raloxifene reduces the risk of spine fractures but not nonvertebral or hip fractures. Raloxifene should not be used in women who have had a venous thromboembolic disease. Since raloxifene does not reduce hip or nonvertebral fracture, it should not be used as a first-line agent. However, it may be used for patients with low BMD in the spine but not in the hip.
Bazedoxifene, another SERM, reduces new vertebral fractures but not in nonvertebral fractures. This selective estrogen receptor modulator is approved in a combination pill with conjugated equine estrogen. In a study by Lindsay et al., the combination of bazedoxifene and estrogen showed a statistically significant increase in BMD at multiple sites over 2 years compared with a placebo.
Bisphosphonates bind to hydroxyapatite in bone, particularly at sites of active bone remodeling, and reduce the activity of bone-resorbing osteoclasts. Three agents (alendronate, risedronate, and zoledronate) are considered “broad-spectrum” with broad antifracture efficacy (spine, hip, and nonvertebral fracture risk reduction) and should be considered as initial options for all patients in the absence of contraindication.,, Patients with “high fracture risk,” such as postmenopausal women with no prior fractures and moderately low T-scores, can be started on oral agents. Injectable agents should be considered as initial therapy for those patients who are at very high fracture risk. A meta-analysis by Sichun et al. showed that bisphosphonates reduced the hip fracture with an overall effect (respiratory rate [RR]: 0.66; 95% confidence interval [CI]: 0.56–0.77; zoledronic acid: RR: 0.60; 95% CI: 0.46–0.78; risedronate: RR: 0.74; 95% CI: 0.59–0.94; and alendronate: RR: 0.61; 95% CI: 0.40–0.95). Orally administered bisphosphonates should be taken after a prolonged fast (usually fasting overnight and taken in the morning soon after arising) and swallowed with a full glass of water. In patients with the active esophageal disease, orally administered bisphosphonates should be used with caution. Bisphosphonates should be used with caution in patients with chronic kidney disease (glomerular filtration rate <30 mL/min for risedronate and ibandronate or <35 mL/min for alendronate).
Injectable and nasal spray recombinant are approved by the FDA to treat postmenopausal osteoporosis. Calcitonin does not reduce hip or nonvertebral fracture risk. As more efficacious agents are available for the treatment of osteoporosis, calcitonin should be limited. Calcitonin also has an analgesic effect, and therefore, short-term prescriptions are often given to patients with acute painful vertebral fractures in hopes of an analgesic effect.
Denosumab is a fully humanized monoclonal antibody that prevents the receptor activator of nuclear factor kappa-B ligand from binding to its receptor, receptor activator of nuclear factor kappa-B, thereby reducing the differentiation of precursor cells into mature osteoclasts and decreasing the function and survival of activated osteoclasts. A meta-analysis by Houchen et al. showed that denosumab improved BMD significantly more than bisphosphonate treatment at the lumbar spine, total hip, and femoral neck at 12 and 24 months. Denosumab is given as a 60 mg subcutaneous injection every 6 months. When treatment with denosumab is stopped after 2 or 8 years, BMD decreases rapidly. Multiple vertebral fractures upon stopping denosumab therapy have been reported. Drug holiday from denosumab is not recommended due to this potential increased fracture risk. If treatment is discontinued, patients should be transitioned to alternative antiresorptive therapy.
Anabolic agents (abaloparatide and teriparatide)
Abaloparatide and teriparatide are considered “anabolic” agents. They are used for women with postmenopausal osteoporosis who are at high risk of fracture or have failed previous osteoporosis therapy, glucocorticoid-induced osteoporosis, and treatment of osteoporosis in men. Both abaloparatide and teriparatide increase BMD and reduce the risk of vertebral and nonvertebral fractures. When treatment with teriparatide is stopped, bone density declines quickly, and hence, the use of bisphosphonates or denosumab should be considered when treatment with these anabolic agents is stopped.
Romosozumab is a new monoclonal antibody directed against sclerostin. Blocking sclerostin binding to osteoblasts allows osteoblast activity to increase. Romosozumab can be used as a “rescue drug” for patients at very high fracture risk. It can be considered an option for patients previously treated with teriparatide or abaloparatide.
Serial BMD testing should be done to determine when to initiate treatment and monitor the response to treatment. For patients on treatment or with a baseline evaluation near a fracture intervention threshold, BMD can be tested every 1–2 years. Pharmacologic and nonpharmacologic treatments for osteoporosis aim to prevent fractures by improving bone strength, preventing falls, and reducing the impact force of falls.
| Conclusion|| |
India is the world's second-largest developing economy and second-most populous country, with 1.2 billion people. Life expectancy now stands at 67 years, but this is predicted to rise to 71 years by 2025 and 77 years by 2050. Osteoporosis is a significant concern for this population. A timely diagnosis of osteoporosis, evaluation of BMD, and early treatment can reduce the global health burden of osteoporotic fracture. Sources estimated that in 2013, 50 million people in India were either osteoporotic or osteopenic. Widespread Vitamin D deficiency has been demonstrated unambiguously throughout India in people of all ages. In India, osteoporosis is not a national health priority. The nutritional program focused on school children to supply vitamins and minerals, particularly Vitamin D and calcium, significantly influencing osteoporosis. Food fortification with Vitamin D should be made a general government policy. The importance of diet and lifestyle strategies in achieving peak bone mass/childhood adolescent bone health should be emphasized more. Intensive, long-term awareness and intervention initiatives are required at the school level.
Multicenter, large-scale hip fracture incidence studies are required. The validation of a FRAX tool tailored to India will allow for more efficient use of diagnostic facilities and improved patient selection. DXA scan use has been limited by its accessibility and affordability; QCT is a simple, quick, non invasive tool that has excellent diagnostic accuracy and is readily available. QCT can be used as an alternative tool for diagnosis and treatment of osteoporosis. Multidynamic modalities include lifestyle changes to reduce bone loss and decrease the risk of falls, identify, and treat secondary causes of bone loss and specific treatment for osteoporosis. It is essential to develop strategies for early detection, prompt prevention, and treatment of osteoporosis in both men and women. A timely diagnosis of osteoporosis, evaluation of BMD, and early treatment can reduce the global health burden of osteoporotic fracture. Therefore, increasing awareness among doctors, which increases awareness among the greater population, will effectively prevent this epidemic.
The strengths of the present study are first related to the fact that it includes not only the available evidence regarding the risk factors and the crucial elements for diagnosing and treating osteoporosis in men, but also some potential recommendations regarding how to manage this condition in a real-life setting. Second, the present review sheds light on the future possibilities for the diagnosis and treatment of osteoporosis.
However, this study has the limitation of being a narrative review rather than a systematic review, and, consequently, a selection study and information bias could not be excluded from the study. Consequently, this study does not aim to change the medical practice on the basis of literature evidence.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]