Can an eating disorder cause a low serum alkaline phosphatase level?

Can Eating Disorders Cause Low Serum Alkaline Phosphatase?

Yes, eating disorders—particularly anorexia nervosa—can cause low serum alkaline phosphatase (ALP), with approximately 65% of adolescent patients demonstrating ALP levels below the normal range. 1

Epidemiology and Prevalence

• Low alkaline phosphatase is a common biochemical finding in anorexia nervosa, occurring in approximately 65% of adolescent patients with the disorder 1
• In contrast, alkaline phosphatase abnormalities were documented in only 7% of adult anorexia nervosa patients in one series, suggesting age-related differences in presentation 2
• The low ALP appears to be relatively specific to restrictive eating disorders, as it was less commonly observed in other causes of malnutrition such as post-surgical anorexia or malignancy-related cachexia 2

Pathophysiologic Mechanisms

• The low ALP in eating disorders reflects decreased bone turnover and reduced osteoblastic activity secondary to severe malnutrition and hormonal disruption 3
• Energy deficiency leads to suppression of the hypothalamic-pituitary-gonadal axis, resulting in hypoestrogenism in females and hypogonadism in males, both of which impair bone formation 3
• Low energy availability (typically <30 kcal/kg fat-free mass/day) triggers metabolic adaptations that reduce energy expenditure and disrupt bone metabolism 3
• The combination of nutritional deficiency and hormonal suppression creates a state of low bone turnover, manifesting biochemically as reduced bone-specific alkaline phosphatase 3

Clinical Context and Associated Findings

• Low ALP in eating disorders typically occurs alongside other metabolic abnormalities including decreased total protein (93% of patients), hypoglycemia (85%), and reduced globulins (78%) 2
• Patients may also demonstrate elevated liver enzymes (AST, ALT, GGT) paradoxically alongside low ALP, reflecting hepatic dysfunction from malnutrition rather than cholestatic disease 2, 4
• Hypophosphatemia is another common finding, particularly during refeeding, and can become severe enough to cause hemolytic anemia and cardiac changes 5
• Zinc deficiency frequently coexists with eating disorders and may contribute to low ALP, as zinc is a cofactor for alkaline phosphatase enzyme activity 6

Diagnostic Implications

• When evaluating unexplained low ALP in young patients, particularly females, eating disorders should be included in the differential diagnosis 1
• The combination of low ALP with low body weight, amenorrhea (in females), and other signs of malnutrition strongly suggests anorexia nervosa 3
• Initial psychiatric evaluation should include quantification of eating behaviors, weight control methods (restriction, purging, excessive exercise), and assessment of body image disturbance 3
• Laboratory assessment should include a complete metabolic panel, complete blood count, and consideration of bone-specific markers if bone health is a concern 3

Clinical Significance for Bone Health

• Low ALP in the context of eating disorders signals impaired bone formation and increased fracture risk, particularly concerning in adolescents who have not yet achieved peak bone mass 3
• Osteopenia and reduced bone mineral density are common complications, with bone density associated with adherence to nutritional therapy 3
• Premenopausal women with eating disorders and low BMD (Z-score ≤ -2.0) require evaluation to exclude secondary causes and should be considered for referral to an osteoporosis specialist 3
• The relationship between low ALP and fracture risk in young patients with eating disorders is not as well-defined as in older populations, but the marker reflects underlying bone pathology 3

Management Considerations

• Treatment requires a multidisciplinary approach including medical, psychiatric, psychological, and nutritional expertise to address both the eating disorder and its metabolic complications 3
• For adolescents and emerging adults with anorexia nervosa, family-based treatment is recommended to normalize eating behaviors and restore weight 3
• Nutritional rehabilitation should include adequate energy, protein, calcium, vitamin D, and consideration of zinc supplementation if deficiency is documented 3, 6
• Monitoring of ALP during recovery can serve as a marker of improving bone turnover as nutritional status and hormonal function normalize 1

Important Caveats

• Not all patients with eating disorders will demonstrate low ALP, and the absence of this finding does not exclude the diagnosis 2
• Low ALP may normalize relatively quickly with refeeding, but bone density recovery takes much longer and may never fully normalize if peak bone mass was not achieved 3
• During refeeding, severe hypophosphatemia can develop and requires close monitoring and supplementation to prevent life-threatening complications 5
• The presence of elevated liver enzymes alongside low ALP should not be misinterpreted as cholestatic liver disease; this pattern is characteristic of malnutrition-related hepatic dysfunction in eating disorders 2, 4