8.1 Clinical Risk Factors & Secondary Causes of Osteoporosis
Key Takeaways
Hyperparathyroidism is an ISCD indication for forearm DXA. The one-third radius can show a lower T-score than the lumbar spine in primary hyperparathyroidism.
In CKD-MBD, DXA can help assess fracture risk if it will affect treatment. It cannot determine bone turnover.
Type 2 diabetes can increase fracture risk even when areal BMD is preserved. Review prior fractures and fall risk as well as the DXA result.
Bone loss after bariatric surgery can reflect altered loading and nutrition. Calcium absorption can fall after Roux-en-Y gastric bypass even when vitamin D status is optimized.
In axial spondyloarthritis, inspect PA spine images for syndesmophytes and apply site-specific validity criteria before interpreting the BMD.
Connect the clinical clue to the assessment
A low bone mineral density (BMD) result or a low-trauma fracture can reflect several contributors. Medical conditions can coexist with age-related or postmenopausal bone loss. Ask which findings could change site selection, interpretation, further testing or treatment safety. A DXA pattern can guide the workup, but it rarely establishes the cause on its own.
Endocrine disorders
In primary hyperparathyroidism (PHPT), chronically inappropriate parathyroid hormone (PTH) secretion can increase bone turnover. The cortical-rich one-third radius may show a greater deficit than the lumbar spine. Relative preservation of spine areal BMD is common enough to recognize, but patients can have deficits at other sites and fracture risk even when the spine result is reassuring. ISCD includes hyperparathyroidism among the indications for forearm BMD. The Fifth International Workshop recommends evaluating the lumbar spine, hip and distal one-third radius when assessing skeletal involvement in PHPT. Interpret the imaging and the biochemical diagnosis separately.
For example, a 61-year-old postmenopausal woman with established PHPT has valid T-scores of −1.1 at the spine, −1.8 at the total hip and −2.9 at the non-dominant one-third radius. The radius is an indicated diagnostic region and is the lowest valid result. This pattern is consistent with cortical involvement. It neither establishes a fixed order of loss at other sites nor measures PTH activity. See calcium, PTH and urine interpretation for the biochemical distinction between PHPT and other causes.
| Medical condition | Clue and densitometry implication |
|---|---|
| Thyrotoxicosis | Thyroid hormone excess can increase bone turnover. Review thyroid history, including possible excess replacement. Low TSH prompts interpretation with free T4 or T3 and the clinical setting. ISCD does not list hyperthyroidism alone as a forearm indication. |
| Hypogonadism | Loss of sex steroid support can contribute to bone loss. Assess menstrual or gonadal history, surgery, medicines and other causes. In men with suspected hypogonadism, evaluate symptoms and confirm low morning fasting testosterone before classifying the cause with gonadotropins. |
| Cushing syndrome | Sustained cortisol excess can compromise bone formation and increase vertebral fracture risk. Review exogenous steroid exposure first. Progressive proximal weakness, easy bruising or wide violaceous striae can support targeted endocrine testing. A normal-range or low-mass DXA result does not exclude a fracture. |
ISCD Adult Official Positions · Fifth PHPT Workshop · American Thyroid Association guideline · Endocrine Society testosterone guideline · Endocrine Society Cushing guideline
Diabetes and fracture risk
Type 1 and type 2 diabetes both increase fracture risk. In type 1 diabetes, low BMD or structural deficits may contribute. A UK cohort found that fracture risk varied by age, sex and site. Avoid applying one relative risk across the lifespan.
In type 2 diabetes, higher measured BMD can coexist with higher fracture risk. In cohorts of older adults, femoral neck T-score and FRAX still predicted fracture. At similar T-scores or conventional FRAX probabilities, adults with diabetes had higher observed risk. A valid DXA result remains useful alongside fracture history and clinical risk.
Peripheral imaging studies suggest that cortical and trabecular differences may contribute in some groups. For example, one cohort found higher average tibial cortical porosity in women with type 2 diabetes than in controls, with no group difference in estimated failure load. The women with diabetes and prior atraumatic fracture showed additional structural deficits compared with those without fracture. Site and subgroup matter. A DXA scan does not measure cortical pores or identify the cause of a specific fracture.
Review fall history, vision, peripheral neuropathy and treatment-related hypoglycemia when relevant. A person with preserved BMD can still need evaluation after a low-trauma fracture. Use an applicable clinical assessment and document any validated FRAX adjustment separately from the conventional probability.
Type 1 diabetes cohort · Type 2 diabetes DXA and fracture outcomes · Type 2 diabetes HR-pQCT cohort · Diabetes-related fall risk
Malabsorption and inflammatory disease
Consider celiac disease with unexplained low BMD, nutritional deficiency, anemia or suggestive gastrointestinal history. Celiac disease can present without prominent gastrointestinal symptoms. An appropriate serology and, in most adults, diagnostic evaluation with duodenal biopsies can identify an enteropathy. Low BMD alone cannot diagnose malabsorption. In inflammatory bowel disease, inflammation, nutrition, reduced activity and glucocorticoid exposure can all contribute. ECCO recommends DXA for patients with inflammatory bowel disease who are at high risk for osteoporosis.
Bone loss after bariatric surgery
Risk varies by procedure and patient. Roux-en-Y gastric bypass can reduce calcium absorption even with adequate vitamin D status, and postoperative weight loss changes skeletal loading. Sleeve gastrectomy can also be associated with bone loss. Review fracture history, dietary intake and relevant biochemical results. See DXA after bariatric surgery for decisions about acquisition and interpretation.
Calcium absorption study · Gastric bypass and sleeve cohort
ACG celiac guideline · ECCO extraintestinal manifestations guideline
Chronic kidney disease, blood disorders and rheumatologic disease
Chronic kidney disease–mineral and bone disorder (CKD-MBD) can include biochemical abnormalities, bone abnormalities and calcification. KDIGO recommends considering calcium, phosphate and PTH trends together. PTH and bone-specific alkaline phosphatase can help assess turnover when values are markedly high or low. For patients with CKD G3a–G5D and evidence of CKD-MBD or osteoporosis risk, DXA can help assess fracture risk if the result will affect treatment. A DXA value cannot distinguish high-turnover renal bone disease from low-turnover disease. KDIGO advises considering CKD progression and the magnitude and reversibility of biochemical abnormalities when choosing treatment in CKD-MBD with low BMD or fragility fracture, with bone biopsy considered when it would affect decisions.
Myeloma can cause focal lytic disease and pathologic fractures. Unexplained anemia, kidney impairment, hypercalcemia, persistent focal pain or suspicious imaging can prompt a targeted evaluation. An isolated low DXA result or compression fracture without lytic lesions does not meet the myeloma bone lesion criterion. Systemic mastocytosis is another possible cause of otherwise unexplained skeletal fragility. A raised baseline tryptase can be a clue and has other causes. It cannot establish the diagnosis alone.
Rheumatoid arthritis has its own FRAX input, separate from oral glucocorticoid exposure. For axial spondyloarthritis, review PA spine images for syndesmophytes and other sources of projection bias. The 2019 ACR guideline conditionally supports assessing both spine and hip even with syndesmophytes or fusion, while EULAR advises hip assessment with selected additional spine methods in patients with radiographic lumbar syndesmophytes. Apply the ISCD technical criteria to each region. In a 52-year-old man with extensive syndesmophytes overlapping the PA spine ROI and a technically valid femoral neck T-score of −2.6, the hip can support the diagnosis. The elevated apparent PA spine result cannot measure the trabecular density beneath the ossification.
KDIGO CKD-MBD guideline · IMWG myeloma criteria · Mast cell criteria consensus · FRAXplus calculator · ACR axial spondyloarthritis guideline · EULAR imaging recommendations
A 61-year-old postmenopausal woman with primary hyperparathyroidism has valid T-scores of −1.1 at the spine, −1.8 at the total hip and −2.9 at the non-dominant one-third radius. Which interpretation fits these findings?
The one-third radius is an indicated diagnostic region, and its lower result is consistent with cortical involvement.
The radius result must be discarded because the spine and hip are measurable.
The DXA pattern alone establishes that the calcium elevation is caused by primary hyperparathyroidism.
The spine result rules out skeletal involvement from primary hyperparathyroidism.
A 66-year-old man with type 2 diabetes sustains a proximal humerus fracture after a fall from standing height. His valid spine, total hip and femoral neck T-scores are +0.4, −0.6 and −0.8. How should these results inform the fracture evaluation?
The spine result rules out further hip or vertebral fracture risk.
The scores describe preserved areal BMD. Review the low-trauma fracture, fall risk and other clinical factors even with those scores.
The scores prove that a fall from standing height was high-energy trauma.
The hip T-score identifies cortical porosity as the specific cause of the fracture.
A 52-year-old man with axial spondyloarthritis has extensive syndesmophytes overlapping his PA lumbar spine DXA region, which yields a T-score of +1.8. His femoral neck scan is technically valid and has a T-score of −2.6. Which interpretation is appropriate?
Use the higher lumbar T-score because it reflects the patient’s trabecular bone density.
Average the spine and femoral neck T-scores for diagnostic classification.
Recognize the possible upward effect of projected ossification at the spine and use the valid femoral neck result for classification.
Defer interpretation at both sites because syndesmophytes invalidate femoral neck DXA.
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