INTRODUCTION — Osteoporosis is a common disease that is characterized by low bone mass with microarchitectural disruption and skeletal fragility, resulting in an increased risk of fracture. The World Health Organization (WHO) has defined diagnostic thresholds for low bone mass and osteoporosis based upon bone mineral density (BMD) measurements compared with a young adult reference population (T-score) (table 1).
The initial osteoporosis evaluation includes a history to assess for clinical risk factors for fracture and to evaluate for other conditions that contribute to bone loss, a physical examination, and basic laboratory tests. There are many coexisting medical conditions that contribute to bone loss (table 2). Thus, evaluation for alternative causes of bone loss to detect potentially reversible causes should be considered in those with abnormal initial findings.
Early diagnosis and quantification of bone loss and fracture risk have become more important because of the availability of therapies that can slow or even reverse the progression of osteoporosis.
The clinical manifestations, diagnosis, and evaluation of osteoporosis in men will be reviewed here. The treatment and the epidemiology and etiology of osteoporosis in men are discussed separately. (See "Treatment of osteoporosis in men" and "Etiology of osteoporosis in men".)
CLINICAL MANIFESTATIONS — Osteoporosis has no clinical manifestations until there is a fracture. Many vertebral fractures are asymptomatic. They may be diagnosed as an incidental finding on chest or abdominal radiographs. The clinical manifestations of symptomatic vertebral fractures include pain and height loss. (See "Osteoporotic thoracolumbar vertebral compression fractures: Clinical manifestations and treatment", section on 'Clinical manifestations'.)
Men may also have symptoms of disorders that are known to cause osteoporosis, such as hypogonadism, malabsorption, and hyperparathyroidism (table 2). Although osteoporosis may be clinically silent until fracture occurs, men experience higher mortality than women after sustaining a fragility fracture [1]. (See "Etiology of osteoporosis in men".)
DIAGNOSIS — Osteoporosis is characterized by low bone mass, microarchitectural disruption, and increased skeletal fragility. In all men, a clinical diagnosis of osteoporosis may be made in the presence of a fragility fracture, particularly at the spine, hip, wrist, humerus, and pelvis. In the absence of a fragility fracture, bone mineral density (BMD) assessment by dual-energy x-ray absorptiometry (DXA) is the standard test to diagnose osteoporosis in men ≥50 years, according to the classification of the World Health Organization (WHO) (table 1).
●BMD – The bone densitometry definition of osteoporosis in men is not as well standardized as it is in postmenopausal women [2]. For every standard deviation reduction in BMD, men have a relative risk of fracture that is similar to, or even greater than, the relative risk in women. In contrast, the age-specific prevalence of osteoporosis and fracture is lower in men than in women, and therefore, men have a lower absolute risk for fracture than women at any bone density T-score [3]. (See "Osteoporotic fracture risk assessment", section on 'Dual-energy x-ray absorptiometry (DXA)'.)
•Age ≥50 years – Based upon the similar relationship between BMD and fracture in men and women, the WHO recommends using similar diagnostic thresholds for osteoporosis in men (age 50 and older) as in women (table 1) [4]. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'Bone mineral density'.)
There is some controversy about the choice of reference databases for the calculation of T-scores in men. The International Society for Clinical Densitometry (ISCD) changed their position to be concordant with the WHO, with both organizations now recommending the use of a female reference database for men. However, many centers in the United States continue to use sex-specific reference databases [5]. In this scenario, osteoporosis in men is defined by a value for BMD 2.5 or more standard deviations below the young healthy male reference mean (rather than female reference mean). We have chosen this approach because all of the randomized trials of osteoporosis treatment in men recruited subjects based on T-scores calculated using male normal controls, and therefore, we have treatment efficacy data in this population [6]. (See "Overview of dual-energy x-ray absorptiometry", section on 'Reference databases'.)
•Age <50 years – The ISCD recommends that BMD measurements alone should not be used to diagnose osteoporosis in men younger than 50 years [5]. In men below age 50 years with low BMD (Z-score ≤-2.0), we diagnose osteoporosis if there is a history of a fragility fracture and, possibly, if other risk factors for osteoporosis (such as glucocorticoid therapy, hypogonadism, or hyperparathyroidism) are present.
CANDIDATES FOR BONE DENSITY TESTING — We do not perform routine testing in men based solely on age. Instead, we suggest targeted BMD testing in men with:
●Clinical manifestations of low bone mass:
•History of low trauma (fragility) fractures
•Loss of more than 1.5 inches in height
•Radiographic osteopenia
●Disorders that increase the risk of developing osteoporosis (table 2) (see "Osteoporotic fracture risk assessment", section on 'Clinical risk factor assessment' and "Etiology of osteoporosis in men", section on 'Etiology'), such as:
•Hypogonadism (particularly in men receiving gonadotropin-releasing hormone [GnRH] agonist therapy for prostate cancer)
•Glucocorticoid use
•Hypercalciuria
•Primary hyperparathyroidism
•Intestinal disorders associated with malabsorption (eg, celiac disease)
Measuring BMD in men solely because they are above a certain age is controversial. Some groups, such as the National Osteoporosis Foundation (NOF), International Society for Clinical Densitometry (ISCD), and the Endocrine Society recommend BMD testing for all men older than 70 years and in men 50 to 70 years when risk factors are present. This recommendation is supported by data suggesting that total hip bone density predicts fractures as well or better in males than in females [3,7]. Other data, however, do not support routine BMD screening for men based solely on age. In general, fracture data from clinical trials of osteoporosis therapies are quite limited in men, so that there is less certainty that treatment of men who are identified by routine screening will benefit from therapy. Evidence related to screening for osteoporosis and recommendations by expert groups is reviewed in more detail separately. (See "Screening for osteoporosis in postmenopausal women and men", section on 'Recommendations by expert groups' and "Treatment of osteoporosis in men", section on 'Choice of therapy'.)
Skeletal site to measure — Fracture risk can be predicted by measurement or estimation of BMD at many skeletal sites. However, the preferred site for measurement of bone density and the number of sites to measure are debatable and may vary according to the clinical situation. This topic is discussed in greater detail elsewhere. (See "Screening for osteoporosis in postmenopausal women and men", section on 'Skeletal site to measure' and "Osteoporotic fracture risk assessment", section on 'Skeletal site to measure'.)
In men who are candidates for BMD testing, we suggest dual-energy x-ray absorptiometry (DXA) measurements of the spine and hip because fractures at these sites have the greatest impact on patients' health. Measurement of hip BMD also has the highest predictive value for hip fracture. In addition, if pharmacologic therapy is planned, measurement of spine BMD is useful as it shows less variability and can detect responses to therapy earlier than hip BMD. We make the diagnosis according to the lowest T-score measured.
Osteophytes and vascular calcifications are common in aging men and often interfere with the assessment of BMD at this site. In this setting, measurement of hip BMD alone is sufficient. If degenerative changes limit interpretation of BMD measurements of both the spine and hip, forearm DXA should be assessed. In addition, forearm BMD measurements may be more sensitive for bone loss in men who are undergoing androgen deprivation therapy for prostate cancer [8].
EVALUATION — The initial evaluation should include history and physical examination, which may provide an explanation for low bone mass (eg, hypogonadism, glucocorticoid excess), routine biochemical tests to uncover renal or hepatic disease, and a complete blood count, serum testosterone, calcium, alkaline phosphatase, 25-hydroxyvitamin D (calcidiol), and 24-hour urine calcium and creatinine (table 3).
Men who have abnormalities on the initial laboratory testing, have suspicious findings on history and physical examination, or who have unexplained low bone mass after the initial evaluation may also require additional laboratory tests (table 3), such as:
●Parathyroid hormone to screen for primary hyperparathyroidism – We typically measure this in men with hypercalcemia, hypercalciuria, or history of renal stones. Some clinicians prefer to measure parathyroid hormone in all men with osteoporosis as part of the initial evaluation.
●Estradiol – In adult men with acquired hypogonadism, estrogen deficiency may contribute more to bone loss than does androgen deficiency, particularly if levels are below 10 to 15 pg/mL [9]. Accurate measurement of such levels of estradiol is best performed using mass spectroscopy.
●Tissue transglutaminase antibodies to screen for celiac disease – We typically measure this in men who have a low 25-hydroxyvitamin D level and/or low urinary calcium. Some experts recommend these tests in all men with idiopathic osteoporosis. (See "Diagnosis of celiac disease in adults".)
●TSH – We measure thyroid-stimulating hormone (TSH) in men who are taking levothyroxine, or if there are clinical findings suspicious for hyperthyroidism (eg, palpitations, heat intolerance, tremor). (See "Bone disease with hyperthyroidism and thyroid hormone therapy".)
Additional testing for more rare conditions associated with osteoporosis should be performed in selected clinical settings:
●Serum and urine protein electrophoresis to uncover a hematological or myeloproliferative disorder – We typically recommend these measurements in men with anemia and/or vertebral compression fractures.
●Urinary cortisol excretion – We typically measure 24-hour urinary free cortisol if clinical manifestations of Cushing's syndrome are present. Some experts recommend measurement of 24-hour urine free cortisol in men with unexplained low bone density or vertebral fractures, even in the absence of traditional clinical manifestations of Cushing's syndrome. (See "Establishing the diagnosis of Cushing's syndrome" and "Epidemiology and clinical manifestations of Cushing's syndrome", section on 'Subclinical hypercortisolism'.)
●Serum tryptase to screen for systemic mastocytosis – We consider performing this measurement in men with fractures, unexplained osteoporosis, or bone pain. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)
●In rare cases, iliac crest bone biopsy after double tetracycline labeling may be useful, particularly for distinguishing osteoporosis from osteomalacia. The clinical availability of bone biopsy is limited.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Osteoporosis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Osteoporosis (The Basics)" and "Patient education: Medicines for osteoporosis (The Basics)")
●Beyond the Basics topics (see "Patient education: Osteoporosis prevention and treatment (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Osteoporosis is a silent disease until fracture occurs. Complications of fractures include pain, deformity, disability, and loss of height. (See 'Clinical manifestations' above.)
●For men ≥50 years of age, the World Health Organization (WHO) has established diagnostic thresholds for low bone mass and osteoporosis based upon bone mineral density (BMD) measurements of the hip (table 1). A dual-energy x-ray absorptiometry (DXA) T-score ≤-2.5 is consistent with osteoporosis, whereas a T-score between -1.0 and -2.5 is osteopenia. We use a male reference database for calculating T-scores in men. (See 'Diagnosis' above.)
●For men younger than 50 years, BMD measurements alone should not be used to define osteoporosis. In young men with low BMD (Z-score ≤-2.0), we diagnose osteoporosis if there is a history of a fragility fracture and, possibly, if other risk factors for osteoporosis (such as glucocorticoid therapy, hypogonadism, or hyperparathyroidism) are present. (See 'Diagnosis' above.)
●We suggest targeted BMD testing in men rather than routine testing based solely on age (Grade 2C). Some expert groups recommend screening men based on age alone (eg, 70 years or above). (See 'Candidates for bone density testing' above and "Screening for osteoporosis in postmenopausal women and men", section on 'Candidates for BMD testing'.)
We typically measure BMD in men with clinical manifestations of low bone mass, such as radiographic osteopenia, history of low trauma fractures, loss of more than 1.5 inches in height, as well as in those with risk factors for fracture, such as long-term glucocorticoid therapy, hypogonadism, primary hyperparathyroidism, and intestinal disorders (table 2). (See 'Candidates for bone density testing' above.)
●The goal of the evaluation of men with low bone mass (T-score below -2.0) or fragility fracture is to rule out secondary causes (table 2). Many secondary etiologies of osteoporosis can be determined on history and physical examination. (See 'Evaluation' above.)
●In addition, most men with low bone mass or fragility fracture should have basic laboratory testing. Initial laboratory studies should include a complete blood count, biochemistry profile, 25-hydroxyvitamin D, testosterone, and measurement of urinary calcium excretion (table 3), particularly if there is no clear explanation for their low BMD.
Based on the results of the history, physical examination, and basic laboratory testing, more extensive testing may be indicated. (See 'Evaluation' above.)
