Osteoporosis Lab Test Panel

This osteoporosis panel includes:

• Serum total calcium, albumin (to calculate albumin adjusted calcium) and phosphorus as part of a CMP panel to detect conditions associated with hypercalcemia such as primary hyperparathyroidism or hypocalcemia and consequent secondary hyperparathyroidism causing bone loss
• Serum creatinine and estimated glomerular filtration rate (GFR) as part of the CMP panel are useful to detect renal failure which can affect bone health. 
• Serum alkaline phosphatase (ALP) as part of a CMP panel. ALP measurement is useful to detect conditions including Paget's disease, metastatic bone disease and osteomalacia, etc.
• Vitamin D nutrition should be determined by measuring serum 25-hydroxy vitamin D [25(OH)D]. Although there is controversy about the optimum level of 25(OH)D for bone health; while 50 nmol/L is considered acceptable
• Parathyroid Hormone (PTH) measurement would be required if serum calcium is abnormal, to help investigate the cause of the calcium abnormality.
• Ultra-sensitive Estradiol. Low estradiol in men and women has been linked to bone loss.
• Phosphorus. An increased phosphorus with decreased calcium suggests either hypoparathyroidism or renal disease. A decreased phosphorus and an increased calcium suggests hyperparathyroidism or sarcoidosis. When both calcium and phosphorus are decreased diagnostic considerations include malabsorption, vitamin D deficiency and renal tubular acidosis. Increased phosphorus and normal or increased calcium suggests Milk-alkali syndrome or hypervitaminosis D.

What is Osteoporosis?

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone among the elderly.  Bones that commonly break include the vertebrae in the spine, the bones of the forearm, and the hip. Until a broken bone occurs there are typically no symptoms. Bones may weaken to such a degree that a break may occur with minor stress or spontaneously. After the broken bone heals, the person may have chronic pain and a decreased ability to carry out normal activities.

What Tests Can Diagnose Osteoporosis?

Absolute fracture risk in individual subjects is calculated by the use of algorithms which include bone mineral density (BMD), age, gender, history of prior fracture and other risk factors. This review describes the laboratory investigations into osteoporosis which include serum calcium, phosphate, creatinine, alkaline phosphatase and 25-hydroxyvitamin D and estradiol. Parathyroid hormone (PTH) is measured in patients with abnormal serum calcium to determine its cause. Other laboratory investigations such as thyroid function testing, screening for multiple myeloma, and screening for Cushing's syndrome, are performed if indicated. Measurement of bone turnover markers (BTMs) is currently not included in algorithms for fracture risk calculations due to the lack of data.

What Can Cause Osteoporosis?

Osteoporosis may be due to lower-than-normal maximum bone mass and greater-than-normal bone loss. Bone loss increases after menopause due to lower levels of estrogen. Osteoporosis may also occur due to a number of diseases or treatments, including alcoholism, anorexia, hyperthyroidism, kidney disease, and surgical removal of the ovaries. Certain medications increase the rate of bone loss, including some antiseizure medications, chemotherapy, proton pump inhibitors, selective serotonin reuptake inhibitors, and glucocorticosteroids. Smoking, and too little exercise are also risk factors. Osteoporosis is defined as a bone density of 2.5 standard deviations below that of a young adult. This is typically measured by dual-energy X-ray absorptiometry (DEXA).

Hypogonadal (low testosterone) states can cause secondary osteoporosis. These include Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia nervosa, andropause, hypothalamic amenorrhea or hyperprolactinemia. In females, the effect of hypogonadism is mediated by estrogen deficiency. It can appear as early menopause (<45 years) or from prolonged premenopausal amenorrhea (>1 year). Bilateral oophorectomy (surgical removal of the ovaries) and premature ovarian failure cause deficient estrogen production. In males, testosterone deficiency is the cause (for example, andropause or after surgical removal of the testes).

Endocrine disorders that can induce bone loss include Cushing's syndrome, hyperparathyroidism, hyperthyroidism, hypothyroidism, diabetes mellitus type 1 and acromegaly, and adrenal insufficiency.

Malnutrition, parenteral nutrition, and malabsorption can lead to osteoporosis. Nutritional and gastrointestinal disorders that can predispose to osteoporosis include undiagnosed and untreated coeliac disease (both symptomatic and asymptomatic people), Crohn's disease, ulcerative colitis, cystic fibrosis, surgery (after gastrectomy, intestinal bypass surgery or bowel resection) and severe liver disease (especially primary biliary cirrhosis).  People with lactose intolerance or milk allergy may develop osteoporosis due to restrictions of calcium-containing foods. Individuals with bulimia can also develop osteoporosis. Those with an otherwise adequate calcium intake can develop osteoporosis due to the inability to absorb calcium and/or vitamin D. Other micronutrients such as vitamin K or vitamin B12 deficiency may also contribute.

What Lab Tests Help to Diagnose Causes of Osteoporosis?

Laboratory investigations in patients with osteoporosis are undertaken to rule out or to detect common causes of osteoporosis in order to treat them. Further targeted investigations may be performed if indicated by clinical presentation, or if the first line investigations are normal but the severity of osteoporosis is unusual for the age and gender. The following first-line measurements may be routinely indicated in the investigation of patients with osteoporosis:

• Serum total calcium, albumin (to calculate albumin adjusted calcium) and phosphorus as part of a CMP panel to detect conditions associated with hypercalcemia such as primary hyperparathyroidism or hypocalcemia and consequent secondary hyperparathyroidism causing bone loss; although albumin adjustment for serum calcium is not universally performed, this practice may be useful to correct total calcium measurements skewed by abnormal albumin levels. Alternatively, ionized calcium measurement gives a more accurate measure of calcium homeostasis.
• Serum creatinine and estimated glomerular filtration rate (GFR) as part of the CMP panel are useful to detect renal failure which can affect bone health. 
• Serum alkaline phosphatase (ALP) as part of a CMP panel. ALP measurement is useful to detect conditions including Paget's disease, metastatic bone disease and osteomalacia, etc. Total ALP is adequate for demonstrating gross increases in bone formation such as those found in most patients with active Paget's disease, osteomalacia, fracture healing or metastatic bone disease, but is not sensitive enough to detect changes in bone remodeling seen in most cases of uncomplicated osteoporosis. Although gamma-glutamyl transpeptidase (GGT) is suggested by some to distinguish an increase in liver ALP from bone ALP, this is neither sensitive nor specific for this purpose. If changes in bone formation need to be determined with sensitivity or distinguished from an increase in total ALP due to liver disease, a specific bone formation marker such as PINP could be measured.
• Vitamin D nutrition should be determined by measuring serum 25-hydroxy vitamin D [25(OH)D]. Although there is controversy about the optimum level of 25(OH)D for bone health; while 50 nmol/L is considered acceptable, others have suggested 75 nmol/L as desirable for optimum bone health [27, 28]. If the higher cut-off is used, then the vast majority of menopausal women (76.8%) would be considered to have sub-optimal vitamin D nutrition.
• Parathyroid Hormone (PTH) measurement would be required if serum calcium is abnormal, to help investigate the cause of the calcium abnormality.
• Ultra-sensitive Estradiol. Low estradiol in men and women has been linked to bone loss.
• Phosphorus. An increased phosphorus with decreased calcium suggests either hypoparathyroidism or renal disease. A decreased phosphorus and an increased calcium suggests hyperparathyroidism or sarcoidosis. When both calcium and phosphorus are decreased diagnostic considerations include malabsorption, vitamin D deficiency and renal tubular acidosis. Increased phosphorus and normal or increased calcium suggests Milk-alkali syndrome or hypervitaminosis D.

Other More Detailed Tests Depending on Specific Conditions (Not included):

 A full examination of blood and erythrocyte sedimentation rate (ESR) would be useful for general health and for inflammatory diseases which often increase bone loss. Serum protein electrophoresis and free light chains in older patients would be useful to exclude multiple myeloma which causes major bone loss. Other secondary causes such as thyrotoxicosis can be excluded with thyroid function tests, and in men hypogonadism is screened with a serum testosterone. In women, the diagnosis of menopause is made clinically and does not warrant estradiol measurement. If Cushing's syndrome is suggested clinically, then screening tests could be performed: 24 hr urine cortisol, midnight salivary cortisol or overnight dexamethasone suppression test. Rarer conditions, if suspected, could be specifically tested; e.g. celiac disease (which is commonly seen in people of European ancestry, but also in parts of Africa, the Middle East and South Asia) with tissue transglutaminase antibody (together with IgA) or systemic mastocytosis with serum tryptase and/or urine methyl histamine. BTMs are not routinely recommended for the assessment of osteoporosis for the reasons stated above. However, if treatment for osteoporosis is to be initiated and monitoring with BTMs is intended, baseline measurement of fasting morning s-CTX and/or s-PINP may be undertaken.

Reference:

Current Recommendations for Laboratory Testing and Use of Bone Turnover Markers in Management of Osteoporosis. Ann Lab Med. 2012 Mar; 32(2): 105–112.