Bone mineral tests and DXA interpretation

At a glance

• Read calcium, phosphate, ALP, PTH and vitamin D together: the pattern, not any single value, gives the diagnosis.
• PTH is the hinge in hypercalcaemia: raised or inappropriately normal means PTH-mediated; suppressed means look for PTHrP, vitamin D excess or bone destruction.
• 25(OH)D is the test for vitamin D status. 1,25(OH)2D is for a small set of PTH-independent problems.
• Bone turnover markers (PINP and CTX) monitor treatment adherence and response; they don't diagnose osteoporosis.
• DXA gives areal BMD at spine and hip. Use the lowest valid T-score from L1 to L4, total hip or femoral neck, and check the images for artefacts before believing the number.

The biochemistry

Test	Typical adult range	What it tells you
Corrected calcium	2.10 to 2.60 mmol/L	Corrected = measured + 0.02 × (40 − albumin g/L)
Ionised calcium	About 1.15 to 1.30 mmol/L	Use in ICU, acid-base disturbance, very abnormal albumin, CKD
Phosphate	0.75 to 1.50 mmol/L	Low in PTH excess, vitamin D deficiency, FGF23 excess, refeeding
ALP	About 30 to 110 U/L	Bone (with normal GGT) or liver; high in growth, Paget disease, osteomalacia, metastases, healing fractures
PTH	About 1.5 to 7.0 pmol/L	Assay-dependent; interpret with calcium and eGFR
25(OH)D	50 nmol/L or more is adequate	Mild deficiency 30 to 49, moderate 12.5 to 29, severe under 12.5 nmol/L
Urine calcium	Under about 7.5 mmol/day (men), 6.25 (women)	Ca/Cr clearance ratio under 0.01 suggests FHH

• 25(OH)D testing is Medicare-funded only for defined risk groups (osteoporosis, malabsorption, dark skin or covered dress, housebound, drugs that lower vitamin D). Details are in Osteomalacia and vitamin D deficiency.
• 1,25(OH)2D is often normal or high in deficiency, because secondary hyperparathyroidism drives renal 1-alpha-hydroxylase. Measure it for PTH-independent hypercalcaemia (sarcoidosis, TB, lymphoma), hypophosphataemic disorders and vitamin D-dependent rickets.
• PTHrP is for hypercalcaemia with a suppressed PTH. It is raised in humoral hypercalcaemia of malignancy (squamous lung, head and neck, renal, breast, ovarian), and rarely in pregnancy and lactation. See Hypercalcaemia of malignancy.
• PTH in CKD rises progressively from eGFR under about 45 mL/min; KDIGO targets 2 to 9 times the upper limit in dialysis. See CKD-mineral and bone disorder.

Patterns

Condition	Calcium	Phosphate	PTH	25(OH)D	ALP
Primary hyperparathyroidism	High	Low or low-normal	High or inappropriately normal	Normal or low	Normal or high
FHH	Mildly high	Normal	Normal or mildly high	Normal	Normal
Vitamin D deficiency, osteomalacia	Low or normal	Low	High	Low	High
Malignancy (PTHrP)	High	Low	Suppressed	Normal	Variable
Granulomatous disease	High	Normal or high	Suppressed	Normal (1,25 high)	Normal
Hypoparathyroidism	Low	High	Low or inappropriately normal	Normal	Normal
Pseudohypoparathyroidism	Low	High	High	Normal	Normal
CKD-MBD	Low or normal	High	High	Often low	Normal or high
Paget disease	Normal	Normal	Normal	Normal	Isolated high
Hypophosphatasia	Normal or high	Normal or high	Normal or low	Normal	Low

Pitfall: diagnosing normocalcaemic primary hyperparathyroidism without first correcting vitamin D deficiency and excluding CKD, thiazides and lithium. Most "normocalcaemic PHPT" is secondary.

Detail on hypercalcaemia workup and the FHH ratio is in Hypercalcaemia and hypocalcaemia and Primary hyperparathyroidism.

Bone turnover markers

• Formation: serum PINP (procollagen type 1 N-propeptide), bone-specific ALP, osteocalcin.
• Resorption: plasma beta-CTX-I (C-terminal telopeptide), TRACP5b.
• The 2025 ESCEO-IOF-IFCC consensus reaffirms PINP and CTX as the reference markers. In advanced CKD, CTX and total PINP (the Roche assay common in Australia) accumulate, though intact PINP doesn't, so bone ALP and TRACP5b are preferred.
• Collection: CTX fasting, before 10 am, same time each visit. PINP has little food or circadian effect.
• Uses: checking adherence and absorption 3 to 6 months after starting an oral bisphosphonate; deciding when to restart after a drug holiday; confirming suppression before stopping denosumab (often with zoledronic acid timing guided by CTX).
• Response: a fall greater than the least significant change (roughly 30% or more) or to below the premenopausal mean (about 35 µg/L for PINP, about 280 ng/L for CTX) is adequate on antiresorptives. On teriparatide or abaloparatide, PINP should rise.
• Confounders: a fracture in the past 6 to 12 months raises markers; so do immobility, pregnancy and lactation. Glucocorticoids lower them.

DXA: what it measures

• Two X-ray beams of different energies separate bone from soft tissue, giving areal BMD in g/cm². Radiation is tiny (about 1 to 10 µSv, less than a day of background).
• T-score: standard deviations from the young adult mean of the same sex (NHANES III white female reference for the hip in both sexes, per ISCD). Used in postmenopausal women and men 50 or over.
• Z-score: compared with age-, sex- and ethnicity-matched peers. Used in premenopausal women, men under 50 and children. Z-score -2.0 or lower is "below the expected range for age" and prompts a search for secondary causes; don't label it osteoporosis.

WHO category	T-score
Normal	-1.0 or higher
Low bone mass (osteopenia)	Between -1.0 and -2.5
Osteoporosis	-2.5 or lower
Severe (established) osteoporosis	-2.5 or lower plus a fragility fracture

Treatment thresholds, FRAX and PBS criteria are in Osteoporosis.

Reading a DXA report step by step

1. Check the images. Are L1 to L4 correctly labelled (count from the lowest rib-bearing vertebra)? Is the hip internally rotated so the lesser trochanter is barely visible?
2. Look for artefacts that raise spine BMD: osteophytes and facet arthritis (common after 65), aortic calcification, vertebral compression fractures, scoliosis, laminectomy or metal, recent barium or contrast, calcium tablets in the gut.
3. Exclude abnormal vertebrae. Drop any vertebra with a T-score more than 1.0 different from its neighbour. At least 2 vertebrae are needed; one vertebra can't be used for diagnosis.
4. Take the lowest valid T-score from lumbar spine, total hip and femoral neck. Don't use Ward's area or the greater trochanter alone.
5. Use the forearm (33% radius) when spine or hip can't be read, in primary hyperparathyroidism (cortical loss), or in patients over the table weight limit.
6. Compare with previous scans only on the same machine, using the centre's least significant change (about 3% spine, 5% total hip). The spine (L1 to L4) is preferred for monitoring when it is evaluable; use the total hip when degenerative change makes the spine unreliable, which is common in older people.
7. Vertebral fracture assessment (VFA) with lateral DXA imaging can detect silent vertebral fractures, which change the diagnosis and PBS eligibility. Trabecular bone score (TBS) adjusts FRAX for bone texture, especially in type 2 diabetes and glucocorticoid use.

Pitfall: treating a "normal" spine T-score of -0.4 in an 80-year-old with severe spondylosis as reassuring while the femoral neck is -2.7.

Medicare and PBS rules that depend on DXA

• Medicare funds DXA from age 70 (repeat at 2 years if T-score is between -1.5 and -2.5, at 5 years if above -1.5), and at any age with a minimal trauma fracture or a listed condition such as glucocorticoids, early menopause, hypogonadism, primary hyperparathyroidism, chronic liver or kidney disease, rheumatoid arthritis, malabsorption or thyrotoxicosis.
• PBS antiresorptive criteria without a fracture need a T-score of -2.5 or lower at age 70 or over, or -1.5 or lower on prednisolone 7.5 mg daily (or equivalent) for 3 months or more.
• Aboriginal and Torres Strait Islander people have earlier hip fractures with higher mortality, and DXA is often hard to reach in remote areas. Use FRAX and clinical risk, and don't let missing DXA delay treatment after a fragility fracture.

Worked examples

Example 1. A 68-year-old woman: L1 to L4 T-score -1.1 (L1 -2.4, L2 -2.3, L3 -0.1, L4 +0.6), total hip -2.1, femoral neck -2.6, with osteophytes at L3 to L4 on the image. L3 differs from L2 by 2.2, more than 1.0, so it is excluded. L4 differs from L3 by only 0.7, so the 1.0 rule alone doesn't remove it; it goes because of the visible degenerative change. The L1 to L2 T-score is approximately -2.3 (the software recalculates it from combined BMC and area rather than averaging). The femoral neck T-score of -2.6 is the lowest valid result: osteoporosis. She is under 70 without a fracture, so PBS-subsidised therapy needs a qualifying fracture or other criterion, though the RACGP guideline supports treatment.

Example 2. A 55-year-old man with a wrist fracture: calcium 2.30 mmol/L, phosphate 0.62 mmol/L, ALP 210 U/L (GGT normal), PTH 14.2 pmol/L, 25(OH)D 18 nmol/L. Low phosphate, high ALP and secondary hyperparathyroidism with moderate vitamin D deficiency: osteomalacia. Check coeliac serology. Replace vitamin D and calcium before any bisphosphonate, which can cause hypocalcaemia here.

Example 3. A 73-year-old woman on oral alendronate for 6 months: fasting CTX 520 ng/L (baseline 560). Barely any fall. Ask how she takes it (fasting, upright, 30 minutes before food), and screen for coeliac disease; switch to zoledronic acid or denosumab if adherence can't be fixed.

How it's tested

• Biochemical pattern tables: osteomalacia, FHH, PTHrP-mediated hypercalcaemia, hypoparathyroidism.
• DXA report with a spuriously normal spine.
• Which score to use in a 42-year-old woman (Z-score).
• Bone turnover markers for adherence and before stopping denosumab.

Pitfalls

• Measuring 1,25(OH)2D to diagnose vitamin D deficiency.
• Calling a low Z-score in a young person osteoporosis.
• Comparing BMD from two different machines.
• Taking non-fasting CTX samples.
• Starting a bisphosphonate in a patient with a low ALP (hypophosphatasia) or with untreated osteomalacia.
• Ignoring forearm BMD in primary hyperparathyroidism, where cortical bone suffers most.