Diagnosis of osteoporosis

Differential diagnosis

Remember that not all fractures are osteoporotic. The differential diagnosis of fractures includes:

Many of these may be diagnosed from radiographs, bone scans, or magnetic resonance imaging studies. Sometimes bone biopsies are necessary.

Physical findings

Patients with decreased bone density usually have no specific abnormal physical findings. Those with vertebral compression fractures will have kyposis, protruding abdomen and height loss. Back tenderness is usually only present after an acute fracture. Gait speed and grip strength are often reduced in patients who have or are about to have a hip fracture. Visual acuity should be checked in geriatric patients because it is a risk factor for falling.

Secondary causes of osteoporosis may be associated with physical findings, such as nodular thyroid, hepatic enlargement, cushingoid features, skin rashes, jaundice, abnormal dentition, and findings of hypogonadism.

Xray findings

Sometimes decreased bone density ("demineralization") can be detected by xray, but bones can appear normal despite loss of 30% of bone mineral. On the other hand, bones in over-exposed films can appear demineralized when they aren't. Bone density measurements are much more accurate than xrays in determining bone density.

The "Singh index" of the proximal femur correlates with bone density. The trabeculae of the femur are lost in sequence, depending on the physical stresses to the bone, so the remaining trabecular pattern indicates the severity of bone loss.

Fractures are discussed in the clinical description page.

Laboratory tests

These are 2014 costs from our lab
Chemistry panel $45
Serum calcium $28
24hr urine calcium $26
Serum phosphate 23
Creatinine $23
Magnesium $31
Alkaline phosphatase $26
CBC $27
TSH $50
Testosterone $70
25OH vitamin D $34
PTH, intact $79
N-telopeptide $56
Bone-specific alk.phos. $51
Protein electrophoresis$30

For an uncomplicated patient with osteoporosis, a lab workup would be a chemistry panel (electrolytes, bicarbonate, creatinine, albumin, calcium, alkaline phosphatase), CBC, phosphate, TSH and 24-hour urine calcium. Males should have testosterone measured. The main purpose of laboratory tests is to check for secondary causes of osteoporosis such as cases of renal or hepatic failure, anemia, acidosis, hypercalciuria, and abnormalities of calcium/phosphate. A nice paper by Tannenbaum, C. documents the utility of these kind of blood tests.

Alkaline phosphatase is an inexpensive method of checking for osteoblastic activity. It is not as sensitive or specific as newer "bone markers" but it will detect moderate to severe osteomalacia or Paget's disease.

The 24-hour urine calcium measurement is frequently ignored but it is a valuable and inexpensive test. High levels are seen in idiopathic hypercalciuria, and low levels suggest malabsorption. The test should be done on a patient's customary calcium intake.

Protein electrophoresis should be done whenever a patient presents with new fractures. Both serum and urine tests should be done because some patients with myeloma have abnormalities in only one.

Urine cortisol for 24 hours can be helpful in patients with Cushingoid features or totally unexplained osteoporosis. Low bone density at the spine but not at the hip can be seen with high cortisol. A dexamethasone suppression test is also used when this is suspected.

Testosterone should be measured in men with osteoporosis. Men may have low testosterone without other clinical symptoms. If testosterone is low, then further work-up is needed. In females who are postmenopausal, it is not helpful to measure levels of estrogens or testosterone. However, in young females, evaluation of estradiol and FSH are indicated if periods are not regular.

Vitamin D is often recommended for patients who have osteoporosis. The 25-OH-vitamin D is the metabolite that should be checked (NOT the 1,25-(OH)2-vitamin D), and values should be between 20 and 50 ng/ml. In patients who are generally healthy and are taking the recommended intake, it is not necessary to check the vitamin D unless the urine calcium is high or low. However, if there is a condition associated with low vitamin D or the patient has severe disease, it should be measured. More information on the page about vitamin D.

Parathyroid hormone is not routinely checked because it is expensive, but when the calcium is abnormal or the patient has serious osteoporosis without other explanation then it should be measured.

Bone specific biochemical markers are discussed on the next page.

Sprue tests, such as antibodies to tissue transglutaminase, are indicated in a patient with low urine calcium, signs of diarrhea and weight loss, or unexplained anemia with osteoporosis. Celiac sprue can cause osteoporosis without any intestinal complaints, although that is somewhat unusual.

Tryptase is elevated in patients with mastocytosis, which is a very rare cause of osteoporosis. This is not routinely measured but could be checked in patients with skin rashes, allergies, or bee sting allergies.

Genetic tests for osteogenesis imperfecta (mutations in Type I collagen) can now be done on blood samples in patients with a strong family history of multiple fractures, especially multiple childhood fractures. This should be done when physical examination reveals blue sclera.

Updated 2/9/2014, reviewed 2/10/16