eMedicine Specialties > Rheumatology > Metabolic and Bone Disease

Osteoporosis: Differential Diagnoses & Workup

Author: Dana Jacobs-Kosmin, MD, Attending Physician, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center; Clinical Assistant Professor of Medicine, Jefferson Medical College
Coauthor(s): Coburn Hobar, MD, Clinician in Rheumatology, Hobar Health and Wellness, and Anti-Aging & Wellness Center of Sarasota; Sucharitha Shanmugam, MD, Consulting Physician, PMA Medical Specialists, Limerick, PA
Contributor Information and Disclosures

Updated: Sep 30, 2009

Differential Diagnoses

Hyperparathyroidism
Multiple Myeloma
Osteomalacia and Renal Osteodystrophy
Paget Disease

Other Problems to Be Considered

Metastases
Leukemia
Lymphoma
Mastocytosis
Pediatric osteogenesis imperfecta
Scurvy
Sickle cell anemia
Homocystinuria

Workup

Laboratory Studies

Laboratory studies are used to establish baseline conditions or to exclude secondary causes of osteoporosis.

  • CBC count
  • Serum chemistries including calcium, phosphate, creatinine, liver function tests, electrolytes: levels of serum calcium, phosphate, and alkaline phosphatase are usually normal in persons with primary osteoporosis, although alkaline phosphatase levels may be elevated for several months after a fracture.
  • Thyroid-stimulating hormone
  • 25-hydroxyvitamin D [25(OH)D]

Other laboratory studies used to evaluate for secondary causes include the following:

  • Twenty-four-hour urine calcium to assess for hypercalciuria
  • Intact parathyroid hormone
  • Testosterone level (in males)
  • Sedimentation rate
  • Urinary free cortisol and tests for adrenal hypersecretion
  • Serum and urine protein electrophoresis
  • Antigliadin and antiendomysial antibodies for celiac disease
  • Serum tryptase, urine N-methylhistamine for mastocytosis
  • Bone marrow biopsy if a hematologic disorder is suspected

Markers of bone turnover (both formation and resorption) may be elevated in high–bone-turnover states (eg, early postmenopausal osteoporosis) and may be useful in some patients for monitoring early response to therapy. However, further study is needed to determine their clinical utility in osteoporosis management. Some of these biochemical measures include the following:

  • Bone formation markers - Bone-specific alkaline phosphatase, osteocalcin, type I procollagen peptides
  • Bone resorption markers - Urinary deoxypyridinoline and cross-linked N- and C-telopeptide of type I collagen

Imaging Studies

Dual-energy x-ray absorptiometry
Dual-energy x-ray absorptiometry (DXA) is the standard study used to establish or confirm a diagnosis of osteoporosis, to predict future fracture risk, and to assess changes in bone mass over time. DXA is used to calculate bone mineral density (BMD) at the hip and spine. Although measurement at any site can be used to assess overall fracture risk, measurement at a particular site is the best predictor of fracture risk at that site. Whenever possible, the same technologist should perform subsequent measurements on the same patient using the same machine. This method can be used in both adults and children. Factors that may result in a falsely high bone density determination include spinal fractures, osteophytosis, and extraspinal (eg, aortic) calcification.

The National Osteoporosis Foundation and the International Society for Clinical Densitometry (ISCD) recommend that BMD be measured in the following patients:

  • Women aged 65 years and older and men aged 70 years or older, regardless of clinical risk factors
  • Younger postmenopausal women and men aged 50-70 years with clinical risk factors for fracture
  • Women in menopausal transition with a specific risk factor associated with increased risk for fracture (ie, low body weight, prior low-trauma fracture, use of a high-risk medication)
  • Adults with fragility fractures
  • Adults who have a condition (eg, rheumatoid arthritis) or who take a medication (eg, glucocorticoids, ≥5 mg/d for ≥3 mo) associated with low bone mass or bone loss
  • Anyone being considered for pharmacologic therapy for osteoporosis
  • Anyone being treated for osteoporosis (to monitor treatment effect)
  • Anyone not receiving therapy in whom evidence of bone loss would lead to treatment

Bone density data from a DXA are reported as T-scores and Z-scores. T-scores represent the number of standard deviations (SD) from the mean bone density values in healthy young adults, whereas Z-scores represent the number of SD from the normal mean value for age- and sex-matched controls.

  • Criteria by the World Health Organization (WHO) define a normal T-score value as within 1 SD of the mean bone density value in a healthy young adult.
    • T-score of -1 to -2.5 SD indicates osteopenia.
    • T-score of less than -2.5 SD indicates osteoporosis.
    • T-score of less than -2.5 SD with fragility fracture(s) indicates severe osteoporosis.
  • For each SD reduction in BMD, the relative fracture risk is increased 1.5-3 times.
  • The WHO BMD diagnostic classification should not be applied to premenopausal women, men younger than 50 years, or children. Z-scores adjusted for ethnicity or race should be used, with Z-scores of -2.0 or lower defined as "below the expected range for age" and those above -2.0 being "within the expected range for age." The diagnosis of osteoporosis in these groups should not be based on densitometric criteria alone.

WHO fracture risk algorithm24

This algorithm (www.shef.ac.uk/FRAX/) was developed to calculate the 10-year probability of a hip fracture and the 10-year probability of any major osteoporotic fracture (defined as clinical spine, hip, forearm, or humerus fracture) in a given patient. These calculations account for femoral neck BMD and other clinical risk factors, as follows:

  • Age
  • Sex
  • Personal history of fracture
  • Low body mass index
  • Use of oral glucocorticoid therapy
  • Secondary osteoporosis (ie, coexistence of rheumatoid arthritis)
  • Parental history of hip fracture
  • Current smoking status
  • Alcohol intake (3 or more drinks per day)
This algorithm is most useful in identifying patients with osteopenia who are most likely to benefit from treatment. The National Osteoporosis Foundation recommends osteoporosis treatment in patients with a low bone mass in whom a US-adapted WHO 10-year probability of a hip fracture is 3% or more or in whom the risk for a major osteoporosis-related fracture is 20% or more.7

Vertebral fracture assessment

Densitometric spine imaging can be performed at the time of DXA scanning to detect vertebral fractures. Vertebral fracture assessment (VFA) should be considered when the results may influence clinical management of the patient.25

Radiography

 Obtain radiographs of the affected area in symptomatic patients. Lateral spine radiography can be performed in asymptomatic patients in whom a vertebral fracture is suspected, in those with height loss in the absence of other symptoms, or in those with pain in the thoracic or upper lumbar spine.

  • Radiographs may show fractures or other conditions such as osteoarthritis, disk disease, or spondylolisthesis.
  • Plain radiography is not as accurate as BMD testing. Approximately 30-80% of bone mineral must be lost before radiographic lucency becomes apparent on radiographs.26

Additional imaging modalities

  • Quantitative CT scanning: This is used to measure BMD as a true volume density in g/cm3, which is not influenced by bone size. This technique can be used in both adults and children but assesses BMD only at the spine. Other limitations include significant radiation exposure, high cost, and possible interference by osteophytes.
  • Peripheral DXA: This is used to measure BMD at the wrist. Peripheral DXA may be most useful in identifying patients at very low fracture risk who require no further workup.
  • Quantitative ultrasonography of the calcaneus: This is a low-cost portable screening tool. This method does not involve radiation but is not as accurate as other methods and cannot be used to monitor the response to treatment because of its lack of precision.

Procedures

Undecalcified iliac bone biopsy with double tetracycline labeling is rarely necessary but may be considered when no cause for osteoporosis is apparent, therapy is not eliciting a response, or osteomalacia is suspected. Tetracycline double labeling is a process used to calculate data on bone turnover. In this procedure, patients are given tetracycline, which binds to newly formed bone. This appears on biopsy samples as linear fluorescence. A second dose of tetracycline is given 11-14 days after the first dose; this appears on a biopsy sample as a second line of fluorescence. The distance between the two fluorescent labels can be measured to calculate the amount of bone formed during that interval.

Histologic Findings

Histologic examination of osteoporotic bone may reveal generalized thinning of trabeculae and irregular perforation of trabeculae, reflecting unbalanced osteoclast-mediated bone resorption.20

More on Osteoporosis

Overview: Osteoporosis
Differential Diagnoses & Workup: Osteoporosis
Treatment & Medication: Osteoporosis
Follow-up: Osteoporosis
Multimedia: Osteoporosis
References
Further Reading
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Keywords

osteoporosis, type 1 osteoporosis, type 2 osteoporosis, postmenopausal osteoporosis, senile osteoporosis, primary osteoporosis, secondary osteoporosis, osteoporotic fracture, hip fracture, PMO, male osteoporosis, bisphosphonates, bone loss, brittle bones, dowager hump, dual-energy x-ray absorptiometry, DXA, estrogen deficiency, fragile bones, fragility fracture, hormone replacement therapy, HRT, hypogonadism, low bone mass, osteoblasts, osteoclasts, osteocytes, osteopenia, raloxifene, receptor activator nuclear factor-kappa B ligand, RANK, RANKL, secondary hyperparathyroidism, thin bones, vertebral compression fracture, vertebral fracture assessment, VFA, vitamin D deficiency

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Contributor Information and Disclosures

Author

Dana Jacobs-Kosmin, MD, Attending Physician, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center; Clinical Assistant Professor of Medicine, Jefferson Medical College
Dana Jacobs-Kosmin, MD is a member of the following medical societies: American College of Rheumatology
Disclosure: Nothing to disclose.

Coauthor(s)

Coburn Hobar, MD, Clinician in Rheumatology, Hobar Health and Wellness, and Anti-Aging & Wellness Center of Sarasota
Coburn Hobar, MD is a member of the following medical societies: American Academy of Anti-Aging Medicine and American College of Rheumatology
Disclosure: Nothing to disclose.

Sucharitha Shanmugam, MD, Consulting Physician, PMA Medical Specialists, Limerick, PA
Sucharitha Shanmugam, MD is a member of the following medical societies: American College of Rheumatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Elliot Goldberg, MD, Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

 
 
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