Osteoporosis has a tremendous negative impact on the physical, emotional, and mental wellbeing of postmenopausal women. It is a chronic disease affecting one in three women and one in five men over the age of 50 years . It causes impaired bone density and quality, hence the name porous. As a result, women having this condition are more susceptible to fracture risk from a non-trivial slip, fall, or even spontaneously. As per WHO (World Health Organization), it is defined as having a bone density of less than 2.5 SD (standard deviation) as compared to an average healthy population of the same age and sexuality.
WHO Criteria for Osteoporosis using BMD (Bone Marrow Density)
Classification according to T-Score value:
Normal: greater than -1.0
Osteopenia: -1.0 to -2.5
Osteoporosis: less than -2.5
Severe or established osteoporosis: less than -2.5 plus history of fragility fractures
Osteoporosis is commonly encountered in older women with no underlying risk factors. However, this does not necessarily mean that it is attributed only to old age.
Many diseases have strong evidence to be considered as risk factors attributing to the development of osteoporosis, even in the young female population. These include conditions like hyperthyroidism, hyperparathyroidism, celiac disease, chronic kidney disease, and autoimmune disorders like rheumatoid arthritis, SLE (systemic lupus erythematosus), ankylosing spondylosis. Smoking is an important modifiable risk factor besides high alcohol intake.
It is always a good clinical practice to advise women to quit smoking and reduce their alcohol intake.
Vitamin D is essential for managing bone strength and calcium absorption. It is a significant factor considered as an additional risk for osteoporosis in countries lacking tropical weather, which is vital for vitamin D synthesis.
Other contributing factors to the development of osteoporosis are the judicious use of certain medications, known as secondary risk factors for osteoporosis. Important to mention are corticosteroids, thyroxine, antacids, and chemotherapies, especially aromatase inhibitors.
One of the critical health hazards is osteoporosis, with over 200 million affected people worldwide. It has more prevalence in postmenopausal women with around 25 to 30 percent of its prevalence in the United States and equally in Europe. Besides the actual prevalence, there had been a tremendous impact due to increased life expectancy and a more aged population.
A previous history of fracture is, by itself, a very significant risk factor for future fractures. Those already sustained a low trauma fracture in the past have over 80 percent probability for a new one. Similarly, those who had a history of vertebral fracture have over two-fold increased risk of hip fracture and roughly 1.5 fold distal forearm fracture risk.
Ethnicity also has a strong influence on the prevalence of osteoporosis, with co-relation to bone mineral density (BMD).
Bone metabolism is a complex mechanism that revolves around the needful bone turnover involving bone formation (osteoblastic activity) and resorption (osteoclastic activity). This cycle continues throughout life and has phases of rapid bone formation to phases of increased resorption. This complex process takes weeks to months. It can be simplified for the purpose of a better understanding of bone mineralization and formation.
We need to understand that this whole process goes through a continuous phase of activation, resorption, formation, mineralization, followed by a period of quiescency. These five factors are called stages of bone modeling.
For successful remodeling, the existing bone matrix should be completely removed prior to new bone formation. The other molecular details to mention are beyond the scope of this learning module.
Factors that contribute to osteoporosis are as follows:
Current challenges in treatment with judicious use of oral corticosteroids had led to a very increased surge of osteoporosis from prolonged use of these medications. Steroids decrease the peripheral calcium ion concentration resulting in PTH release and very rapid bone loss, especially in the first three months of steroid use. This also results in impairing bone quality because of increased osteoblastic activity, not able to measure or quantify by normal bone measuring techniques like DEXA scan.
The main histopathological abnormality of an osteoporotic bone is trabecular thinning with defects in the trabeculae, in the form of irregularity, reflecting the role of osteoclastic overactivity in most of the bone samples (from osteoporotic bones).
Osteoporosis has no specific clinical signs and symptoms unless there is a fracture. Some patients may complain of bone aches (hips and feet), but the pain is more of a symptom of osteomalacia. Fracture Risk Assessment Tool (FRAX) is available for evaluating 10-year fracture risk probability, especially hip and other major osteoporotic fractures. FRAX assessment takes into consideration of age, family history, smoking status, steroid use, arthritis, and femoral neck bone density. Common manifestations of osteoporosis include vertebral fracture, hip fracture (about 15% of women), and distal radial fractures. Vertebral fractures are typically incidentally noted on imaging as a majority of them are asymptomatic.
Unfortunately, the screening of women for osteoporosis doesn't have an international following, although, in the United States and Canada, Bone Mineral Density in postmenopausal women greater than 65 years is recommended for screening even without risk factors. There are various risk factors for osteoporosis classified under modifiable and non-modifiable.
In General, the causes of osteoporosis can be simply classified into Primary and Secondary. Primary is generally age-related influenced by hormonal and dietary elements, while secondary osteoporosis is a result of various medical conditions and medications.
Primary: Primary causes of osteoporosis can be further subclassed into Type 1 and Type 2.
Secondary: Certain Medical conditions increase bone remodeling leading to interference or disruption of bone reformation. There is a resultant bone loss as a consequence of imbalance from new bone production and loss. Some of the common conditions promoting osteoporosis are hyperparathyroidism, hyperthyroidism, diabetes, thalassemia, multiple myeloma, intestinal malabsorption, leukemia, Liver disease, metastatic bone disease, Cushing's syndrome, acromegaly, scurvy, and Marfan's syndrome.
In addition to medical conditions, medications that can cause osteoporosis are antacids containing aluminum, heparin, anticonvulsants, thyroxine, and steroid use(cortisone therapy).
Apart from the above-mentioned causes, modifiable risk factors are listed below.
Non-modifiable risk factors include but are not limited to:
1) History of fracture as an adult or in a first-degree relative
2) White race
3) Advanced age/Dementia/Fragility
4) Female sex
Modifiable risk factors include
1) Current cigarette smoking
2) Low BMI
3) Early menopause (less than 45-year-old) or bilateral oophorectomy and prolonged premenopausal amenorrhea (for more than a year)
4) Low dietary calcium intake
6) Recurrent falls
A thorough history is mandatory to identify known risk factors for osteoporosis and osteoporotic fracture, as listed above. Conditions including COPD (chronic obstructive pulmonary disease), asthma, and other rheumatological disorders like giant cell arteritis, polymyalgia, and others with judicious use of steroids for years predispose patients for secondary osteoporotic risk. Risk factors for falls in older patients include poor balance, weakness of muscles and deconditioning, medications with sedative effects, poor vision, or hearing.
Some fractures are picked on incident x-ray findings, especially vertebral. However, there can be associated features of pain, a decrease in height, cord compression features of severe disability in weight-bearing moments from hip fractures. Gait disturbances could also occur as a result of an abnormal pattern of walking and occasional loss of muscle tone and sarcopenia (muscle mass loss)
The initial evaluation should include basic labs to access levels of complete blood count, serum electrolytes, calcium, phosphorus, albumin, total protein, renal, and liver function. Also, thyroid function and 25-hydroxyvitamin D levels should be obtained. Based on the abnormalities detected in basic labs, patients should have additional tests to evaluate for diseases like celiac disease, malignancies, and multiple myeloma. Disorders of calcium and vitamin D malabsorption should be considered. Hormone imbalances like Cushing syndrome and parathyroid hormone abnormalities are also very important in the evaluation of osteoporosis.
Plain X-ray report of low bone density is a strong predictor of osteopenia or osteoporosis but not diagnostic. Changes in plain radiograph showing osteopenia, wedging in vertebrae can be a clue of underlying fracture risk.
DEXA Bone Density Scan
The most common test used for the measurement of bone health and osteoporosis is the DEXA bone density scan (Dual-energy x-ray Absorptiometry). It is a radiological diagnostic test and is universally classified by T and Z scores. T score is the measurement of bone density compared to younger people and estimates the risk of fracture, whereas Z score measures the bone density of the comparable age group. Most guidelines use T score as a standard approach for estimating fracture risk assessment and treatment. T score above -1 is Normal, a score of -1.0 to -2.5 is classified as osteopenia, and anything less than -2.5 is osteoporosis. These numerical values are the standard deviations of comparison. It is important to mention that T-scores are just a clinical guide for treatment and can sometimes vary from case to case basis, e.g., a patient on steroid use for more than six months and expected to be on that for a while is offered treatment with T score of only -1.5, whereas a young female with underlying celiac disease and vitamin D malabsorption with T score of -2.8 might not be offered bisphosphonates before correcting the reversible causes.
Besides the DEXA scan, other radiological tests could be used to support and differentiate the cause of fracture, including pathological and secondary fractures from malignancies. These include conventional radiography, CT (computed tomography (CT) scans, MRI, and bone scan (scintigraphy). Recently, the use of bone turnover markers was introduced as part of monitoring treatment failures or responses. They are not used in isolation as some results are nonspecific, but they could be helpful in complex patient assessments where DEXA scans alone might not be sufficient for decision making. These include serum alkaline phosphatase (ALP) and bone-specific ALP. Serum osteocalcin (a specific marker for osteoblastic function), serum type 1 procollagen, or serum carboxy-terminal collagen crosslinks (CTX) (a marker for bone resorption) are used as treatment response markers. Besides these, there are other bone resorption markers like urinary hydroxyproline, urinary pyridinoline, bone sialoprotein, and few others.
Bone Biopsy, although very specific in identifying the mineralization and microarchitecture of the bone is rarely used for diagnosis of osteoporosis, but are nevertheless included when determining the effects of treatment, bone structure, and turnover in certain clinical contexts. They can establish the safety and efficacy of new treatment modalities if clinically appropriate.
Management of osteoporosis in women could be approached with two aspects, namely lifestyle modifications, and pharmacological therapy. The recommended guidelines are based on fracture risk assessment,co-morbidities, and any history of fragility fractures.
Pharmacological Therapy: After replacing and supplementing adequate calcium and vitamin D, specific medications for osteoporosis could be initiated based on fracture risk assessment using FRAX as suggested by WHO.
As per the National Osteoporosis Foundation (NOF) guidelines, pharmacological therapy is initiated in any of the three scenarios:
1. Patient with a history of hip or a vertebral fracture
2. T-score less than or equal to -2.5 at femoral neck or spine
3. T-score between -1 and -2.5 with a 10-year probability of more than 3 percent hip fracture or more than 20 percent probability of osteoporosis-related major fracture.
Bisphosphonates are still considered to be the first-line treatment of osteoporosis, which ranges from oral to intravenous use, the commonest ones include Alendronic acid, risedronate, etidronate, ibandronate, pamidronate, and zoledronate.
Although a precise mechanism of action is unsure, the evidence so far with their use is based on two facts. One, its affinity for hydroxyapatite (an essential constituent of the bone mineral matrix) and second, targeting FPP inhibition (farnesyl pyrophosphate synthase), an important enzyme which eventually prevents the formation of essential signaling proteins for osteoclastic activity reducing bone resorption and overall turnover.
Dosing and route of administration of bisphosphonates depend on the specific medication and the formulation, whether it is an immediate release or delayed-release.
Patients with esophageal motility disorders, including severe hiatal hernia and patients with a history of certain Roux-en-Y gastric bypass surgery, oral bisphosphonates are contraindicated, but intravenous zoledronic acid could be considered.
As the drug has a half-life of over ten years, it can remain for a few years in the body tissues even after stopping. Side effects of bisphosphonate therapy include transient hypocalcemia, bone pain, rare ocular, and renal effects, but few critical side effects of note are osteonecrosis of the jaw and atypical femur fractures after prolonged use.
Other Pharmacological Therapies
Few numbers of patients where the pharmacological treatment has not been helpful, especially in at-risk vertebral fractures, well-known procedures from orthopedics can be helpful for stabilization of fractures and pain relief as well. The two commonest one used is
As with all surgical procedures, they are not risk-free and can lead to bone cement leak, the persistence of pain, allergic reaction to bone cement, infection, paralysis, or rarely pulmonary embolism.
Fractures, especially vertebral and atypical fractures, have wide differentials, particularly in the younger age group, and it needs careful evaluation before considering osteoporosis as a primary diagnosis. Important conditions to rule out are leukemias, lymphomas, melanomas, any metastatic malignancy, especially breasts and ovaries.
Other diseases worth considering are some inborn metabolic, genetic disorders, acquired one's like homocystinuria, sickle cell anemia, mastocytosis, Paget disease, hyperparathyroidism, and scurvy.
Prognosis of this disease is good if detected in early phases of bone loss, which can improve with early initiation of treatment with bisphosphonates. However, if detected after hip fracture, the mortality rate increases significantly by 10 to 15 percent, especially in women aged 80 years or older. Because of high disease prevalence, we need to implement early recognition of this condition with proper efforts for prevention and treatment. The commonest fractures are the hip, followed by vertebral fractures.
The incidence of fractures worldwide is, 80% of the forearm, 75% of humerus, 70% of hip, and 58% of spinal fractures. Hip fractures can be debilitating and associated with chronic pain, disability, reduced mobility, and impaired independence as a result of the same with poor quality of life.
Compared with hip fractures, vertebral fractures are associated with an eight-fold increase with age-related mortality. It can lead to intense back pain with chronicity, a decrease in height, deformity, kyphosis, and even reduced lung function as a result of the same. The presence of vertebral fractures increases the risk of further vertebral and non-vertebral fractures. Women having sustained a vertebral fracture are at risk of additional fracture in 1 to 2 years.
Osteoporotic fractures are associated with high morbidity, increased mortality risk, and significant economic impact. Multiple fractures can severely impair the quality of life in females and can be a severe complication of osteoporosis. Fractures of the hip and spine can limit and disable the patients. Some might have to undergo surgical interventions, including neurosurgical, if fractures cause any spinal canal stenosis or cord compression. Patients with hip fractures have an increased risk of mortality in first-year post fractures.
In the management of osteoporosis, treatment effectiveness is considerably limited by some real and perceived intolerance to the therapies, and also due to poor adherence to recommendations. Data have shown that most patients discontinue the prescribed treatment before the end of the first year. Patient education remains the central theme of considering primary prevention of this condition. Avoidance of modifiable risk factors plus the importance of a healthy diet, exercise, and bone health will remain the cornerstone in care and prevention of this alarmingly raising co-morbidity.
Overall, the coordination of the interprofessional teams is needed to target the issue at the community level, which includes patient education and awareness through general practitioners, community health care nursing professionals, and allied health care workers.
Social services can support in reaching target populations and vulnerable groups, like severely disabled due to old age, dementia, or severe functional impairments.
Nursing staff should actively educate women about the importance of smoking cessation, walking/active lifestyle, and exercise regimes, especially in postmenopausal groups, by providing written information leaflets and referring them to available educational websites.
Referral to specialists is crucial in preventing the development of osteoporosis at secondary levels in patients with non-modifiable risk factors, including autoimmune diseases and long-term steroid use.
Patient education and clear communication among the members of the interprofessional teams are essential to assess and evaluate women presenting with this condition effectively. To achieve the best standard of care for women at risk or even already affected by this condition, interprofessional coordinated care is mandatory.
|||Trevisan C,Alessi A,Girotti G,Zanforlini BM,Bertocco A,Mazzochin M,Zoccarato F,Piovesan F,Dianin M,Giannini S,Manzato E,Sergi G, The Impact of Smoking on Bone Metabolism, Bone Mineral Density and Vertebral Fractures in Postmenopausal Women. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2019 Jul 10 [PubMed PMID: 31350204]|
|||Mitek T,Nagraba Ł,Deszczyński J,Stolarczyk M,Kuchar E,Stolarczyk A, Genetic Predisposition for Osteoporosis and Fractures in Postmenopausal Women. Advances in experimental medicine and biology. 2019 [PubMed PMID: 31309515]|
|||Hiligsmann M,Cornelissen D,Vrijens B,Abrahamsen B,Al-Daghri N,Biver E,Brandi ML,Bruyère O,Burlet N,Cooper C,Cortet B,Dennison E,Diez-Perez A,Gasparik A,Grosso A,Hadji P,Halbout P,Kanis JA,Kaufman JM,Laslop A,Maggi S,Rizzoli R,Thomas T,Tuzun S,Vlaskovska M,Reginster JY, Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF). Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019 Nov [PubMed PMID: 31388696]|
|||[PubMed PMID: 31425945]|
|||Cher EWL,Allen JC,Howe TS,Koh JSB, Comorbidity as the dominant predictor of mortality after hip fracture surgeries. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019 Dec [PubMed PMID: 31451838]|
|||Dardonville Q,Salguiero E,Rousseau V,Chebane L,Faillie JL,Gautier S,Montastruc JL,Carvajal A,Bagheri H, Drug-induced osteoporosis/osteomalacia: analysis in the French and Spanish pharmacovigilance databases. European journal of clinical pharmacology. 2019 Dec [PubMed PMID: 31468068]|
|||Das M,Cronin O,Keohane DM,Cormac EM,Nugent H,Nugent M,Molloy C,O'Toole PW,Shanahan F,Molloy MG,Jeffery IB, Gut microbiota alterations associated with reduced bone mineral density in older adults. Rheumatology (Oxford, England). 2019 Dec 1 [PubMed PMID: 31378815]|
|||[PubMed PMID: 31405768]|
|||Kim HA,Lee HY,Jung JY,Suh CH,Chung YS,Choi YJ, Trabecular Bone Score Is a Useful Parameter for the Prediction of Vertebral Fractures in Patients With Polymyalgia Rheumatica. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2019 May 23; [PubMed PMID: 31174962]|
|||Svedbom A,Hernlund E,Ivergård M,Compston J,Cooper C,Stenmark J,McCloskey EV,Jönsson B,Kanis JA, Osteoporosis in the European Union: a compendium of country-specific reports. Archives of osteoporosis. 2013 [PubMed PMID: 24113838]|
|||van Dort MJ,Driessen JHM,Geusens P,Romme EAPM,Smeenk FWJM,Wouters EFM,van den Bergh JPW, Vertebral bone attenuation in Hounsfield Units and prevalent vertebral fractures are associated with the short-term risk of vertebral fractures in current and ex-smokers with and without COPD: a 3-year chest CT follow-up study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019 Jun 3; [PubMed PMID: 31161317]|
|||Thomasius F,Hadji P, [Influence of hormone or hormone replacement therapy on bone healing]. Der Unfallchirurg. 2019 Jun 6; [PubMed PMID: 31172230]|
|||Adhikary S,Kothari P,Choudhary D,Kumar Tripathi A,Trivedi R, Glucocorticoid aggravates bone micro-architecture deterioration and skeletal muscle atrophy in mice fed on high-fat diet. Steroids. 2019 May 28; [PubMed PMID: 31150681]|
|||Osteoporosis, Childhood Bullying, Rheumatoid Arthritis, Diabetes Counseling, Inhaled Steroids. American family physician. 2019 Mar 15; [PubMed PMID: 30874411]|
|||Löffler MT,Jacob A,Valentinitsch A,Rienmüller A,Zimmer C,Ryang YM,Baum T,Kirschke JS, Improved prediction of incident vertebral fractures using opportunistic QCT compared to DXA. European radiology. 2019 Feb 21; [PubMed PMID: 30790025]|
|||Gutierrez-Buey G,Restituto P,Botella S,Monreal I,Colina I,Rodríguez-Fraile M,Calleja A,Varo N, Trabecular bone score and bone remodeling markers identify perimenopausal women at high risk of bone loss. Clinical endocrinology. 2019 May 29; [PubMed PMID: 31141196]|
|||Howe TE,Shea B,Dawson LJ,Downie F,Murray A,Ross C,Harbour RT,Caldwell LM,Creed G, Exercise for preventing and treating osteoporosis in postmenopausal women. The Cochrane database of systematic reviews. 2011 Jul 6 [PubMed PMID: 21735380]|
|||Eastell R,Rosen CJ,Black DM,Cheung AM,Murad MH,Shoback D, Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. The Journal of clinical endocrinology and metabolism. 2019 May 1 [PubMed PMID: 30907953]|
|||Sun ZW,Li ZY,Yu D,Zhu JY,Zhang YD,Zhu XM, [Bisphosphonate-related osteonecrosis of the jaw complicated with wrist scaphoid osteomyelitis: a case report]. Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology. 2019 Apr 1; [PubMed PMID: 31168992]|
|||Steller D,Herbst N,Pries R,Juhl D,Hakim SG, Positive impact of Platelet-rich plasma and Platelet-rich fibrin on viability, migration and proliferation of osteoblasts and fibroblasts treated with zoledronic acid. Scientific reports. 2019 Jun 5; [PubMed PMID: 31165745]|
|||Xie BP,Shi LY,Li JP,Zeng Y,Liu W,Tang SY,Jia LJ,Zhang J,Gan GX, Oleanolic acid inhibits RANKL-induced osteoclastogenesis via ER alpha/miR-503/RANK signaling pathway in RAW264.7 cells. Biomedicine [PubMed PMID: 31176167]|
|||Haider IT,Simonian N,Saini AS,Leung FM,Edwards WB,Schnitzer TJ, Open-label clinical trial of alendronate after teriparatide therapy in people with spinal cord injury and low bone mineral density. Spinal cord. 2019 Jun 4; [PubMed PMID: 31164732]|
|||Barrionuevo P,Kapoor E,Asi N,Alahdab F,Mohammed K,Benkhadra K,Almasri J,Farah W,Sarigianni M,Muthusamy K,Al Nofal A,Haydour Q,Wang Z,Murad MH, Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis. The Journal of clinical endocrinology and metabolism. 2019 May 1 [PubMed PMID: 30907957]|
|||Saeki C,Oikawa T,Kanai T,Nakano M,Torisu Y,Sasaki N,Abo M,Saruta M,Tsubota A, Relationship between osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in patients with primary biliary cholangitis. European journal of gastroenterology & hepatology. 2020 Jun 16 [PubMed PMID: 32558699]|