Clinical Tests> Bone>

DESCRIPTION

• Bone mineral density (BMD) is a measure of mineral content for a given bone area or volume.
• Osteoporosis is a systemic skeletal disorder characterized by low bone mineral density and microarchitectural deterioration of bone tissue with consequent increase in bone fragility and susceptibility to fracture.
• Bone architecture consists of minerals (calcium, phosphorus) which form hydroxyapatite crystals, as well as type I collagen and other proteins.
• Type 1 diabetes mellitus (T1DM): BMD lower than age-matched healthy population; at higher risk for fracture compared to age-matched population (Schwartz).
• Type 2 diabetes mellitus (T2DM): BMD higher than age-matched healthy population; may be at higher risk for fracture despite higher BMD (Schwartz, Brandi).

ASSAYS

• Dual x-ray absorptiometry (DXA) considered the clinical gold standard for measuring BMD at the lumbar spine, total hip, femoral neck, and forearm.
• DXA quantifies bone mineral content (BMC) in grams and bone area (BA) in centimeters squared, with BMD equalling BMC/BA in grams per centimeters squared.
• Vertebral fracture assessment may also be done for high risk patients.
• Quantitative CT measures volumetric bone density rather than areal density (product of DXA) but is expensive and not used for regular clinical evaluation (Khoo).
• Calcaneal ultrasound, radiographic absorptiometry, and single energy x-ray absorptiometry have all been employed for BMD calculation (Nayak).
• New imaging technologies (MICRO CT and MRI) are in development to better assess bone microarchitecture and quality for clinical use.

INDICATIONS

• No specific guidelines for BMD measurement in type 1 or type 2 diabetes mellitus, necessitating use of guidelines established for the age and sex-matched healthy population.
• The National Osteoporosis Foundation (NOF) recommends BMD screening for women > 65 years-old and men > 70 years-old regardless of fracture risk (Heinemann).
• DXA evaluation should be considered in younger post-menopausal women and men, age 50-70 years, who have additional fracture risk factors. Per NOF, diabetes mellitus is considered an additional fracture risk factor. (Heinemann).
• Other clinical risk factors which may prompt BMD measurement, including a low BMI, family history of hip fracture, tobacco or alcohol abuse, chronic inflammatory disease (rheumatoid arthritis, ulcerative colitis, etc.), long-term steroid or anti-epileptic use, hormonal dysregulation (prolonged vitamin D deficiency, hyperparathyroidism, hypogonadism, hyperthryoidism, Cushing's syndrome, etc.) (Kanis)
• DXA evaluation should be performed in all persons with a fragility fracture (fall from standing height or less resulting in fracture), regardless of age.
• Imaging for persons treated with osteoporosis medications (bisphosphonates, teriparatide, SERMs, etc.) or those considered candidates for therapy.
• Thiazolidenedione use associated with low BMD and fracture

DIFFERENTIAL DIAGNOSIS

•  Bone mineral density defined on a spectrum of normal, osteopenia, and osteoporosis (see Interpretation section)

INTERPRETATION

• DXA BMD reported as a T-score and Z-score at the lumbar spine, total hip, femoral neck, or forearm (may require separate request at some institutions).
• T-score calculated as the mean BMD of < 30 year-old reference population minus patient BMD, divided by the standard deviation (SD) of the young population (Heinemann).
• Z-score calculated as the mean BMD of peers (age and sex-matched) minus patient BMD, divided by the SD of referenced peers.
• Normal bone density is defined as a T-score above -1.0. 
• Osteopenia defined as a T-score between -1 and -2.5. 
• Osteoporosis defined as a T-score less than or equal to -2.5.
• Severe (or established) osteoporosis defined as a T-score < -2.5 in the presence of one or more fragility fractures.
• Changes in BMD evaluated with sequential DXA evaluation, with significant percent change at a specific body site defined by institution and machine standards (Baim).
• In pre-menopausal women and men < 50 years, Z-score should be used, rather than T-score. Z-scores < -2.0 considered low BMD, but should not alone be the basis for treatment decisions.

LIMITATIONS OR CONFOUNDERS

• DXA, quantitative CT, and other noted imaging modalities describe bone quantity, not quality (important in fracture risk)
• DXA accuracy and precision dependent on machine calibration, technologist skill, and appropriate interpretation of BMD data and imaging (Kanis)
• Proper patient positioning on the scanner table is required for accurate BMD, and is the most common error in densiometry testing.
• Those with scoliosis cannot be positioned correctly on the table, invalidating spine BMD measurements.
• Local structural and degenerative changes (osteophytes, compression fractures, aortic calcification, spondylosis, etc.) can falsely elevate BMD at local sites.
• Artifacts including surgical clips, metal jewelry, and radio-opaque tablets will spuriously elevate BMD.
• Obese patients, such as those with T2DM, may not fit properly on the scanning table; half-body DXA scanner may be needed.
• Excessive lean mass and fat mass (obese individuals) at the skeletal region of interest may increase DXA-derived BMD inaccuracies (Bolotin).

EXPERT COMMENTS

• BMD can help predict fracture risk, but it cannot replace clinical judgement and risk factor assessment for people with diabetes. (Brandi).
• Bone density testing 1-2 years following initial screening DXA indicated in people on medication for osteoporosis or those considered at high risk for fracture if medication might be indicated later.
• Fracture risk assessment tool (http://www.shef.ac.uk/FRAX/) uses femoral neck BMD and patient risk factors for osteoporosis into a multivariate model, helping to predict 10-year major osteoporotic and hip fracture; T1DM considered a risk factor for bone loss in the model (Kanis).
• Measurements of bone density measure bone area (DXA) and volume (quantitative CT), are surrogate determinants of bone quality (Khoo).

REFERENCES