Study results show that a routine blood test can reveal a hidden risk of osteoporosis

Study results show that a routine blood test can reveal a hidden risk of osteoporosis

Common blood test results can provide an early indication of bone loss, suggesting that alkaline phosphatase levels could help identify people who might benefit from earlier osteoporosis assessment before fractures occur.

In a study recently published in the journalFrontiers in endocrinologyResearchers investigated whether the routinely measured blood enzyme alkaline phosphatase (ALP) can serve as a marker for osteoporosis.

They found that higher ALP levels were consistently associated with a higher likelihood of osteoporosis, with stronger associations observed in metabolically healthy, younger and female individuals, and identified a potential threshold for recommending further assessments of bone health.

Burden of osteoporosis and need for accessible biomarkers

Osteoporosis is characterized by reduced bone mass and structural deterioration, leading to an increased risk of fractures and significant impact on health and quality of life. As life expectancy increases, the prevalence is increasing worldwide. Because fracture incidence increases dramatically with age, particularly after age 75, there is growing interest in identifying accessible biomarkers that may help detect bone loss earlier.

ALP is produced primarily by bone-forming osteoblasts and hepatocytes and plays a key role in bone mineralization through the breakdown of pyrophosphate. Approximately half of the ALP in blood comes from bone, and bone-specific ALP is largely consistent with total ALP levels in healthy and osteoporotic populations.

Total ALP is inexpensive and widely used in routine health examinations, and researchers have investigated its potential as a surrogate marker of bone health. However, previous results are contradictory: some studies report negative associations between ALP and bone mineral density, others found no clear pattern.

Factors such as sample size, population heterogeneity, reliance on self-reported data, and metabolic or liver diseases affecting ALP further complicate interpretation.

Study population and clinical assessments

The researchers wanted to clarify whether total AP could be a reliable predictor of osteoporosis risk in a large, systematically studied population. They conducted their analysis using cross-sectional data from routine health examination records from a large teaching hospital in Chongqing, China, for the period 2019-2024.

Eligible participants were adults 20 years of age or older who had completed blood AP testing and dual-energy X-ray absorptiometry (DXA) scans of the hip and spine. Records with incomplete information were excluded, and in the case of duplicate entries, only the most recent examination was taken into account.

Osteoporosis was diagnosed according to World Health Organization (WHO) criteria using DXA-T scores, with modified definitions applied to younger adults. Standardized hospital procedures were used to collect anthropometric measurements, blood pressure, liver ultrasound findings, and biochemical markers including glucose, lipids, uric acid, and liver enzymes. The definition of metabolic disorders followed established medical guidelines.

Statistical analyzes included descriptive comparisons, t-tests, chi-square tests, and five logistic regression models that took into account stepwise age, sex, body composition, metabolic markers, and liver function. Restricted cubic spline regression was tested for nonlinear associations between osteoporosis and ALP, while receiver operating characteristic (ROC) analysis assessed the predictive performance of ALP and identified an optimal cutoff using the Youden index.

Participant characteristics and initial associations

Of the 12,835 participants, 9.5% were diagnosed with osteoporosis, and almost all individuals (99%) had ALP levels within the clinical reference range. Participants with osteoporosis had significantly elevated ALP levels. Older people, women and people with lower body weight or larger waist-to-hip ratio were at higher risk of suffering from osteoporosis. Those at higher risk also had higher systolic blood pressure, fasting glucose, total cholesterol and high-density lipoprotein (HDL) levels, while uric acid and liver enzymes were lower. No differences were observed in diastolic blood pressure, triglycerides, or low-density lipoprotein (LDL).

ALP-osteoporosis associations in statistical models

Logistic regression consistently showed that every 1 IU/L increase in ALP was associated with a higher risk of osteoporosis, with unit effect sizes modest but cumulative across the ALP range, and this association remained strong across all adjusted models. Spline analysis showed a mostly linear relationship, but the association leveled off when ALP exceeded 100 IU/L. ROC analysis showed poor to moderate discrimination, with 72 IU/L emerging as the best cutoff for predicting osteoporosis.

Subgroup differences and metabolic influences

Subgroup analyzes revealed stronger statistical associations, rather than a higher absolute risk, in women, younger individuals, and those with normal liver enzymes and healthier metabolic profiles. When liver enzymes were elevated or when glucose or lipid profiles were abnormal, the association weakened or disappeared significantly, suggesting that metabolic and hepatic factors may confound the association between bone status and ALP.

Interpretation, limitations and clinical implications

This study found that higher total serum APP is consistently associated with a higher likelihood of osteoporosis, even within the normal reference range and after adjusting for extensive confounding factors.

The association was strongest in younger women and metabolically healthy individuals, likely because ALP more accurately reflects bone-derived ALP when liver function and metabolic status are normal. Elevated ALP levels may represent a compensatory increase in bone turnover in response to decreasing bone density and are not a direct cause of bone loss. However, when liver damage or metabolic disorders are present, the liver-derived component of ALP may dilute this association.

Strengths include the large sample size, standardized clinical data and detailed subgroup analyses. However, the study relied on a cross-sectional design, drew the population from a single center, and did not include information on physical activity, thyroid status, medication use, and diet, which limited the results.

Overall, an ALP level around 72 IU/L may serve as a preliminary threshold for recommending further bone health assessments, although longitudinal cohort studies are needed to confirm the causal and predictive value.

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