Is a Dual-Energy X-ray Absorptiometry (DEXA) scan recommended for someone with low alkaline phosphatase (alk phos) levels?

DEXA Scan for Patients with Low Alkaline Phosphatase

A DEXA scan is not routinely recommended for patients with isolated low alkaline phosphatase (ALP) levels, but should be performed if there are additional risk factors for bone disease or fracture. 1

Understanding Low ALP and Its Implications

Low serum alkaline phosphatase can be a marker for several conditions, most notably hypophosphatasia (HPP), a rare inherited disorder associated with impaired primary mineralization of osteoid (osteomalacia) 2. This condition is important to identify because:

• HPP may be misdiagnosed as osteoporosis, though they represent different pathologies 2
• Antiresorptive therapy, which is first-line treatment for osteoporosis, is relatively contraindicated in HPP 2, 3
• Persistently low ALP levels should trigger consideration of HPP, which occurs in approximately 3% of patients with low ALP in osteoporosis clinics 2

Diagnostic Algorithm for Patients with Low ALP

1. Confirm persistent low ALP

   • Repeat ALP measurement to determine if the low level is transient or persistent
   • Persistently low ALP (multiple measurements below reference range) warrants further investigation 4

2. Evaluate for secondary causes of low ALP

   • Malnutrition
   • Vitamin and mineral deficiencies
   • Endocrine disorders
   • Medication effects (including antiresorptives) 4

3. Consider specialized testing if persistently low ALP

   • Measure ALP substrates: pyrophosphate, pyridoxal phosphate, or phosphoethanolamine 4
   • Consider genetic testing for ALPL gene mutations if clinical suspicion for HPP is high 4

4. Bone density assessment indications in patients with low ALP:

   a) DEXA scan IS indicated if:

   • Patient has experienced fractures, especially stress fractures or atypical fractures 5
   • Patient has risk factors for osteoporosis (age ≥65 for women, ≥70 for men, or younger with additional risk factors) 1
   • Patient has chronic kidney disease with additional risk factors for fracture 5
   • Patient has experienced height loss or has undocumented vertebral fractures 5

   b) DEXA scan is NOT routinely indicated if:

   • Patient has isolated low ALP without other risk factors for bone disease
   • Patient is young without clinical evidence of bone disease

Important Considerations

• If HPP is suspected, antiresorptive therapy should be avoided as it may potentially worsen bone fragility 3
• In patients with confirmed HPP, DEXA results may not accurately reflect fracture risk as the issue is bone quality (mineralization) rather than quantity 3
• For patients with chronic kidney disease, KDIGO guidelines recommend BMD testing in those with risk factors for osteoporosis, but not solely based on low ALP 5

Pitfalls to Avoid

• Don't assume low ALP is clinically insignificant - persistently low levels should prompt consideration of HPP 2
• Don't automatically prescribe bisphosphonates for patients with low bone density and low ALP without ruling out HPP 3
• Don't rely solely on DEXA T-scores for treatment decisions in patients with low ALP - consider the underlying pathophysiology 4
• Don't miss the opportunity to diagnose HPP - it occurs in approximately 0.3% of osteoporosis clinic patients but 3% of those with low ALP 2

In summary, while low ALP alone is not an indication for DEXA scanning, the presence of additional risk factors for bone disease or fracture should prompt bone density assessment as part of a comprehensive evaluation.