Does age affect alkaline phosphatase (ALP) levels?

Does Age Affect Alkaline Phosphatase Levels?

Yes, age profoundly affects alkaline phosphatase (ALP) levels, with values highest during infancy and adolescence due to active bone growth, declining after skeletal maturity, and rising again modestly in older adults—particularly in women after menopause. 1, 2

Age-Related ALP Patterns Across the Lifespan

Infancy and Early Childhood

• ALP levels are markedly elevated in infants and young children, with bone-specific ALP representing approximately 80–90% of total circulating ALP in this age group, compared to only 50% in adults 2, 3
• Reference ranges in neonates (<15 days) are 110–250 U/L for males and 120–295 U/L for females, reflecting intense skeletal development 4
• From 15 days to 1 year, ranges expand to 80–400 U/L (males) and 90–380 U/L (females), remaining substantially higher than adult values 4

School-Age Children

• ALP levels remain elevated throughout childhood (ages 1–10 years: 105–280 U/L in males, 90–290 U/L in females) due to ongoing bone growth 4
• The predominant isoenzyme in children is of bone origin, with almost all children (99%) exhibiting a second "bone variant" ALP fraction that disappears after age 17 in girls and age 20 in boys 5

Adolescence: Peak ALP Activity

• ALP reaches its highest levels during puberty, with a tetraphasic pattern showing two distinct peaks—one in infancy and a second during adolescence 6
• Girls reach peak bone ALP activity at ages 9–10 years, followed by a gradual decline after age 12 6, 5
• Boys reach peak bone ALP at ages 13–14 years, followed by a steep decline after age 14 6, 5
• During puberty, ALP levels are significantly higher in girls at ages 10–11 years (p=0.02) and in boys at ages 12–13,14–15, and 16–17 years (p<0.001) 6
• Adolescent reference ranges (ages 10–13 years) are 75–300 U/L for males and 90–300 U/L for females 4

Young Adulthood: Post-Growth Stabilization

• After skeletal maturity (ages 15–18 years), ALP declines to 55–150 U/L in males and 60–180 U/L in females 4
• Adult reference ranges (>18 years) stabilize at 55–140 U/L for males and 60–147 U/L for females 4
• During adulthood, bone ALP activity remains constant with no significant sex differences, and liver ALP remains almost unchanged throughout life 5

Older Adults: Age-Related Increases

• Alkaline phosphatase increases by approximately 20% between the third and eighth decades of life 1
• After age 50 years, ALP concentrations become higher in females than males, likely reflecting postmenopausal bone turnover 7
• In postmenopausal women, elevated ALP may originate from bone due to osteoporosis rather than liver disease, as estrogen deficiency drives increased bone isoenzyme production 1, 2

Clinical Implications for Interpretation

Use Age-Specific Reference Ranges

• Laboratories report different upper limits of normal (ULN) for different sex and age groups; absolute values should always be reported and analyzed alongside multiples of ULN 1
• Do not use adult reference ranges for children—age-specific pediatric ranges are essential to avoid misdiagnosis 2, 3
• In children, ALP levels are physiologically 2–3× adult values due to bone growth 8

Distinguish Bone from Hepatic Sources

• Measuring gamma-glutamyl transferase (GGT) or obtaining ALP isoenzyme fractionation is critical to confirm whether elevated ALP originates from bone or liver 1, 2
• In children, total ALP may be sufficient for monitoring bone metabolism due to the predominance of bone isoenzyme, whereas in adults, specific testing for bone ALP is preferred due to more equal distribution between bone and liver sources 2
• Elevated ALP of bone origin is expected in growing children and postmenopausal women with osteoporosis 1, 2

Common Pitfalls to Avoid

• Do not assume all elevated ALP in children is physiologic without checking GGT to exclude cholestatic liver disease 3
• Do not overlook that approximately 20–25% of patients with primary sclerosing cholangitis present with normal ALP, so a normal value does not exclude cholestatic disease 8
• Recognize that in older adults (≥60 years), cholestatic drug-induced liver injury comprises up to 61% of cases, making medication review essential 1, 2