The clinical presentation of osteoporosis in its early stages is asymptomatic and fractures developing as a result of bone fragility are the first manifestation of the disease [1]. Fractures in osteoporosis are seen after low-energy trauma that would otherwise be a minor injury in healthy adults, such as falling from standing height or even smaller exposure of the skeletal system to stress [2]. Fracture of the vertebral body is the most common type of fracture in this patient population, often preceded or accompanied by a progressing kyphosis of the spine [1] [2]. Fractures of the humerus, forearm, femur, and hip are also encountered [1] [2]. They are almost always accompanied by pain, which can be acute when the fracture has occurred, but chronic pain is also reported [1] [2] In addition to fractures, several physical characteristics may be observed. Shortening of the trunk, loss of height (from four to 10 or more centimeters), protrusion of the abdomen, and very long limbs compared to the trunk are some of the main findings [1] [2]. The Thannenbaum or "fir tree phenomenon" is a sign observed in osteoporosis and denotes the presence of skin folds that stretch from the back laterally to the flanks in a "hanging" fashion, resembling a fir tree [2]. Gait abnormalities are also frequent [2].

The diagnostic workup of patients in whom osteoporosis is the possible cause of fractures and associated symptoms must start with a detailed patient history [3]. Because so many disorders (in addition to age-related changes) can cause reduced bone mineral density, it is of essential importance to inquire about the presence of any diseases and identify if any of the drugs that are known induce this phenomenon are being used [3]. One of the key questions that should be asked should be about height loss (either prospective or historical) [3]. Additionally, lifestyle and demographic factors should be taken into account when being suspicious about osteoporosis. The initial workup should start with a detailed physical examination, followed by a complete laboratory assessment - renal and liver function tests (urea, creatinine, liver transaminases), serum electrolytes (calcium and phosphorus), inflammatory markers (C-reactive protein and erythrocyte sedimentation rate, or CRP and ESR, respectively), vitamin D levels, hormonal workup (thyroid stimulating hormone, PTH, gonadal hormones), serum glucose levels, urinary calcium excretion, and alkaline phosphatase (ALP) are some of the studies used to exclude secondary causes [3]. Plain radiography should be employed to assess reported fractures and to evaluate the overall state of the skeletal system, but the key component of the workup is the evaluation of bone mineral density (BMD) [1] [3] [4] [5] [6]. Using X-ray absorptiometry at the hip and spine is a definitive study that establishes the severity of bone fragility and thus determines what is the optimal therapeutic approach [1] [3] [4] [5] [6] [7]. The diagnosis is confirmed when BMD is > 2.5 SDs below the reference mean (T-score ≤ –2.5) of young adult females for both genders [8].

The therapeutic approach to patients with osteoporosis depends on several factors, such as the patient's age, the presence of comorbidities, and the severity of bone fragility. Hence, different modalities can be recommended to different populations [9] [10] [11] [12]:

• Lifestyle changes - Physical activity has a very influential effect on the skeletal system and any form of exercise is strongly recommended for individuals who are at risk or already have osteoporosis [10] [11]. Increasing or maintaining flexibility, muscle strength, and balance are of great benefit for the patient and sports that promote bone growth the most are basketball, gymnastics, dancing, tennis, impact-aerobic, and weight training [2] [10] [11]. Cessation of cigarette smoking, avoiding an underweight status, and sun exposure for at least 30 minutes every day (in order to facilitate vitamin D production) are additional factors that may be influenced by behavior [2].
• Calcium and vitamin D supplementation - Many patients will use calcium and vitamin D supplements either prophylactically or for therapeutic purposes and they have become engraved in the treatment protocol of osteoporosis. Typical doses of vitamin D should range between 400-1200 international units (IU)/day, whereas 1000-1300 mg/day is the usual dose of calcium [2] [9] [10]. If possible, dietary modification should be recommended prior to giving supplements, but many patients cannot reach the necessary daily intake of calcium [2] [10].
• Pharmacologic therapy - Various drugs are used to treat osteoporosis. Alendronate, ibandronate, and risedronate belong to the group of bisphosphonates that inhibit the activity of osteoclasts and thus inhibit bone resorption [2] [6] [11]. They are used as first-line therapy, and apart from mild gastrointestinal side-effects, they are safe to use, but are of limited efficacy in severe renal insufficiency [2] [6] [10] [11]. Denosumab is a recently approved monoclonal antibody that interferes with bone resorption by inhibiting the receptor activator of nuclear factor kappa B ligand and may be freely used in patients who developed renal failure [10]. If these drugs do not improve the status of the patient, raloxifene (only in women), teriparatide (recombinant human PTH), and strontium ranelate are effective alternatives [2] [6] [9] [10] [11].

In the absence of an early diagnosis, osteoporosis carries a significant risk for long-term disability. Studies have shown that up to 50% of all individuals who sustain hip fractures (regarded as the most severe type of injury) never regain previous physical function and mortality rates reach up to 36% within 1 year, according to some reports [1] [2]. Because of the effectiveness of screening procedures that are able to identify early osteoporotic changes, it is imperative to make an early diagnosis and thus prevent injuries that will profoundly decrease the quality of life.

Osteoporosis develops as a result of age-related bone mineral density loss and the term "primary osteoporosis" is often used as a synonym [2] [6] [7]. Many diseases and drugs have shown to either promote or directly influence this process as well and the term "secondary osteoporosis" is used when causes other than aging are involved in the pathogenesis [3] [4] [6] [7]:

• Diseases - A myriad of conditions affect the pathways involved in bone homeostasis and remodeling. Gastrointestinal (celiac disease, inflammatory bowel disease, malabsorptive syndromes, biliary cirrhosis, or previous surgical procedures), endocrine (hyperparathyroidism, Cushing's disease, thyrotoxicosis, diabetes mellitus), hematologic (sickle cell disease, multiple myeloma, leukemias, lymphomas, hemophilia), autoimmune (systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis), are some of the examples [3] [4] [6] [7]. Furthermore, end-stage renal disease (ESRD), hypercalciuria, congestive heart failure, chronic obstructive lung disease, Parkinson's disease, muscular dystrophies, or injury to the spinal cord have also been included in this long list [3] [4] [6] [7].
• Drugs - Aromatase inhibitors (anastrozole, letrozole, exemestane), anticoagulants, long-term use of glucocorticoids (prednisolone), selective serotonin reuptake inhibitors (SSRIs), premenopausal use of tamoxifen, aromatase inhibitors, premenopausal contraceptives (medroxyprogesterone), aluminum-containing antacids, proton-pump inhibitors (omeprazole, pantoprazole), cyclosporin A, thiazolidinediones, cytotoxic chemotherapy drugs (methotrexate, ifosfamide), valproic acid, and gonadotropin-releasing hormone (GnRH) agonists have all been described as potential potential causes [3] [4] [6] [7].
• Genetic disorders - Marfan syndrome, osteogenesis imperfecta, hypophosphatasia, cystic fibrosis, glycogen storage diseases, hemochromatosis, and homocystinuria are examples of genetic diseases that either cause or contribute to osteoporosis [3] [4] [6] [7].

It is estimated that over 200 million people have osteoporosis worldwide and approximately 50% of women and 20% of men will eventually suffer from a fracture as a result of osteoporosis [2] [9]. The list of risk factors that contribute to the development of osteoporosis encompasses disorders of various systems, but also drugs and certain lifestyle actions [3] [4]. Older age, inadequate and insufficient physical activity, low intake of calcium, smoking, immobilization, vitamin D deficiency, low body mass index (BMI), abuse of alcohol, high intake of salt, and excessive falling are some of the main lifestyle factors that are strongly associated with osteoporosis [2] [3] [4] [7] [9]. As stated previously, women are significantly more affected than men, and it is shown that up to 70% of all fractures encountered in this patient population occurs among women over 65 years of age [1] [2]. Caucasians and Asian races seem to be at an increased risk for osteoporosis compared to black men and women [6].

Osteoporosis stems from abnormalities in the bone remodeling process. Under physiological circumstances, a constant balance between bone resorption (mediated by osteoclasts) and bone growth (mediated by osteoblasts) is being maintained [5] [12]. As humans reach older age, this process eventually decreases in efficiency, leading to excessive bone resorption that is not matched by the rate of bone remodeling [5] [12]. Calcium is the key element around which all hormones and other electrolytes revolve when it comes to the skeletal system. More than 99% of all body calcium is stored in bones and a tight regulatory system comprised of vitamin D, parathyroid hormone (PTH), calcitonin, estrogen, and several other elements, ensures that serum calcium levels are constantly within physiological limits, but also aid in maintaining the structural integrity of the skeleton [5] [7] [9] [11]. Deficiency of calcium intake or impaired absorption in the gastrointestinal system, vitamin D deficiency, hyperparathyroidism, or estrogen deficiency (all occuring in older age), lead to a shift of the bone remodeling process toward accelerated bone resorption [5] [7] [9] [11]. Estrogen, considered to be a crucial element for epiphyseal closure in both genders and vital for bone remodeling. Its deficiency, most evidently seen in postmenopausal women, is well-known to contribute to osteoporosis [5] [7] [9] [11]. The end-result is a loss of bone mass and fragility that predisposes patients to falls and pathological fractures, the hallmarks of osteoporosis.

Osteoporosis is a highly controllable disease if recognized in its early stages, which is why a plethora of studies and guidelines focus on screening methods and early detection [2] [3] [6] [11] [12] [13]. Some authors emphasize the need for risk factor evaluation as early as 50 years of age, whereas BMD testing should be performed in women who are older than 65 and in men who are older than 70 years [13]. Furthermore, postmenopausal women between 50-69 years with one or more risk factors (examples being height loss of ≥ 4 or long-term therapy with glucocorticoids) are advised to undergo screening for osteoporosis [6] [13] [14].

Osteoporosis is defined as a disorder of the skeletal system that is distinguished by the loss of bone mass and disruption of the bone microarchitecture that predisposes individuals to fractures and injury [1] [2] [5]. Since its initial description in the 19th century much has been revealed about the pathogenesis, clinical presentation, etiology, diagnosis, and treatment. A rather long list of disorders affecting the hematologic, gastrointestinal, endocrine, autoimmune, and other systems that play a role in the development of osteoporosis has been established (the term secondary osteoporosis is sometimes used), but age is regarded as the most important (primary osteoporosis [3] [4] [6]. However, several lifestyle factors have shown to promote osteoporosis [2] [3] [4] [6] [9]. Insufficient physical activity, cigarette smoking, a very low body mass index (a BMI < 20 is said to double the risk of a femoral fracture in these patients), alcohol abuse, low calcium intake, and high salt intake are identified. The pathogenesis of this skeletal condition arises as a result of a disturbed balance in the bone remodeling process. To preserve the health of the skeletal system, a constant process of resorption and regrowth of the bones is taking place, but once humans reach older age, bone resorption outpaces bone regrowth, resulting in a decreased bone mass and fragility [5] [9] [12]. The clinical presentation of patients with osteoporosis is mainly asymptomatic in the initial stages of the disease, and patients are, unfortunately, recognized when pathological fractures already occur [1] [2]. Fractures of the vertebra, humerus, forearm, or hip can occur and result in severe disability [4]. A thorough diagnostic approach comprised of clinical, laboratory, and imaging studies is necessary to assess the extent and severity of osteoporosis, but also to design optimal therapeutic strategies [3] [4]. Treatment principles include lifestyle modifications (initiation of regular physical activity, cessation of smoking and alcohol abuse), adequate intake of calcium and vitamin D, and pharmacologic therapy with bisphosphonates, hormone therapy (estrogens, parathyroid hormone) or more advanced drugs that target receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor (denosumab). Prevention of osteoporosis is key in reducing morbidity and mortality from fractures and all associated complications and screening guidelines suggest that all adults should be tested for early signs at 50-60 years of age [13].

Osteoporosis is a condition that affects millions of older adults and elderly individuals worldwide. This condition is defined as a progressive loss of bone strength and bone density, mainly as a result of old age (termed primary osteoporosis). In addition to age-related changes of the skeleton, a very large number of diseases (gastrointestinal, hormonal, autoimmune, or genetic) and different drugs (proton pump inhibitors, hormones, antiepileptics, chemotherapy drugs, glucocorticoids, etc.) can induce or promote bone loss. When a specific disorder is responsible for osteoporosis, the term "secondary osteoporosis" is used to denote that older age is not the main culprit. Several risk factors have been established - poor physical activity, high intake of salt, inadequate calcium/vitamin D intake (through food and sun exposure, respectively), cigarette smoking, low body weight and a low body mass index (BMI), female gender (postmenopausal women are substantially more prone to osteoporosis than men), and Caucasian/Asian race. Osteoporosis does not produce any symptoms in its initial stages. Fractures, particularly after falls or low energy trauma that wouldn't normally cause severe injury, are the first recognizable symptom. Unfortunately, these fractures cause marked disability - up to 50% of all patients who suffer from a hip fracture will not fully recover, and up to 36% of patients die within 1 year of this injury. Other frequently encountered fractures involve the spine, the arms and forearms, as well as the femur. Other signs include height loss, kyphosis, shortening of the trunk, and the "fir tree phenomenon", where skin folds extend from the back to the flanks and resemble a fir tree. Because these injuries pose a significant risk for the patient, an early diagnosis is of critical importance. Physicians should conduct a detailed interview during which the underlying cause should be revealed. After a physical examination and a full laboratory workup that aids in excluding other conditions, evaluation of bone mineral density (BMD) is the cornerstone for confirming osteoporosis. Based on the reduction in bone mineral density, different therapeutic approaches are implemented. In milder cases, dietary changes that support an increased intake of calcium through food and vitamin D by exposing the skin to the sun for at least 30 minutes every day, along with physical exercise, are the first steps. Vitamin D and calcium supplementation is often used, whereas bisphosphonates (alendronate, ibandronate, and risedronate) are first-line drugs that are the in patients who require pharmacological therapy. Raloxifene (only in women), teriparatide, strontium ranelate, and denosumab, are other drugs used in therapy. Screening for osteoporosis is advised in women over 65 and in men over 70 years of age, but screening may start as early as 50 years in the presence of one or more risk factors.

1. Lorentzon M, Cummings SR. Osteoporosis: the evolution of a diagnosis. J Intern Med. 2015;277(6):650-661.
2. Baum E, Peters KM. The Diagnosis and Treatment of Primary Osteoporosis According to Current Guidelines. Dtsch Arztebl Int. 2008;105(33):573-582.
3. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014;25(10):2359-2381.
4. Hofbauer LC, Hamann C, Ebeling PR. Approach to the patient with secondary osteoporosis. Eur J Endocrinol. 2010; 162:1009–1020.
5. Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 2005;115(12):3318-3325.
6. Jeremiah MP, Unwin BK, Greenawald MH, Casiano VE. Diagnosis and Management of Osteoporosis. Am Fam Physician. 2015;92(4):261-268.
7. Office of the Surgeon General (US). Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville (MD): Office of the Surgeon General (US); 2004.
8. Nayak S, Olkin I, Liu H, et al. Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis. Ann Intern Med. 2006;144(11):832–841.
9. Ishimi Y. Osteoporosis and Lifestyle. J Nutr Sci Vitaminol (Tokyo). 2015;61 Suppl:S139-141.
10. Gupta A, March L. Treating osteoporosis. Aust Prescr. 2016;39(2):40-46.
11. Kling JM, Clarke BL, Sandhu NP. Osteoporosis Prevention, Screening, and Treatment: A Review. J Womens Health (Larchmt). 2014;23(7):563-572.
12. Das S, Crockett JC. Osteoporosis – a current view of pharmacological prevention and treatment. Drug Des Devel Ther. 2013;7:435-448.
13. Lim LS, Hoeksema LJ, Sherin K; ACPM Prevention Practice Committee. Screening for osteoporosis in the adult U.S. population: ACPM position statement on preventive practice. Am J Prev Med 2009;36:366–375.
14. U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2011;154(5):356–364.