From the Guidelines
Low alkaline phosphatase (ALP) levels should prompt concern about several potential health issues, and if you have low ALP, you should consult with your healthcare provider for proper evaluation, as this could indicate conditions such as malnutrition, protein deficiency, zinc deficiency, magnesium deficiency, or rare genetic disorders like hypophosphatasia. Symptoms to watch for include bone pain, fractures that heal slowly, dental problems, and general weakness. No specific medication directly treats low ALP itself, as treatment targets the underlying cause. For nutritional deficiencies, your doctor might recommend zinc supplements (typically 25-50 mg daily), increased protein intake, or magnesium supplements (300-400 mg daily) 1. Blood tests to check vitamin D, calcium, and phosphate levels are often necessary to determine the exact cause. Low ALP is concerning because this enzyme plays crucial roles in bone formation, liver function, and intestinal health. When levels are insufficient, these processes can be compromised, potentially leading to skeletal problems or indicating other metabolic issues. Unlike high ALP, which is more commonly discussed, low levels often receive less attention but can signal significant health concerns requiring medical investigation. Some key points to consider in the management of low ALP include:
- Monitoring of fasting serum phosphate levels during the titration period between injections, ideally 7–11 days after last injection, to detect hyperphosphataemia 1
- The dose of burosumab should not be adjusted more frequently than every 4 weeks 1
- We recommend that burosumab must not be given in conjunction with conventional treatment, when fasting phosphate levels are within the age-related normal reference range before initiation of treatment or in the presence of severe renal impairment 1
- Normal calcium intake (minimum 1g per day) and a low-sodium diet are recommended to reduce calciuria and support weight control 1
- Pregnancy is a critical moment for bone health, and during pregnancy, 25(OH) vitamin D levels should be monitored and adjusted 1
- Phosphate supplementation might require higher dosages, up to 2,000 mg daily 1
- We suggest supplementing patients with native vitamin D (cholecalciferol or ergocalciferol) in case of vitamin D deficiency; we also suggest ensuring normal calcium intake 1
From the Research
Low Alkaline Phosphatase Concerns
When dealing with low alkaline phosphatase levels, several concerns and potential underlying conditions should be considered:
- Hypophosphatasia, a genetic disorder characterized by low alkaline phosphatase levels, can lead to skeletal pain, chondrocalcinosis, calcific periarthritis, dental problems, and stress fractures 2
- Malnutrition, vitamin and mineral deficiencies, and endocrine disorders can also cause low alkaline phosphatase levels 2
- Certain medications, such as antiresorptives, can lead to low alkaline phosphatase levels 2
- Low alkaline phosphatase levels can be an indicator of underlying conditions, such as kidney bone disease, which is associated with mortality in patients with chronic kidney disease (CKD) 3
Diagnostic Approach
To diagnose the underlying cause of low alkaline phosphatase levels:
- Measuring several alkaline phosphatase substrates, such as pyrophosphate, pyridoxal phosphate, or phosphoethanolamine, may help establish enzyme deficiency 2
- Gene analysis showing a pathogenic variant in the ALPL gene can confirm the diagnosis of hypophosphatasia 2
- Laboratory tests, including alkaline phosphatase levels, should be flagged as abnormal to prompt further investigation 4
Related Conditions
Low alkaline phosphatase levels have been linked to various conditions, including:
- Osteoporosis, which can be treated with vitamin D therapy or active vitamin D analogs 5
- Secondary hyperparathyroidism, which can be caused by impaired intestinal calcium absorption and vitamin D deficiency 5
- Kidney bone disease, which includes bone disorders, mineral disarrays, and vascular calcification 3