Case Report: Cortical bone loss, impaired mineralization, and reduced adiposity contributing to chronic bone pain in SFRP4-related skeletal disease with an ALPL variant

By
Fernando Lizcano
Eliana Avilés
Cristian López
Silvia Maradei-Anaya
Maria Camila Ballesteros-García
Lizeth Bustamante
Fredy Luna
Miguel O’Meara
Alex Valenzuela
June 16, 2026
0 min

Frontiers In Endocrinology

Overview

This case study presents an adult woman with Pyle disease due to a homozygous SFRP4 variant, experiencing severe chronic bone pain. The findings suggest a structural-metabolic interaction involving cortical bone loss, impaired mineralization, and decreased adiposity.

Background

Pyle disease is a rare metaphyseal dysplasia linked to SFRP4 variants, leading to abnormal bone modeling and persistent pain. Understanding the mechanisms behind bone pain in such disorders is crucial for effective management and treatment strategies.

Data Highlights

Parameter	Result
Bone Mineral Density (Lumbar)	Preserved
Femoral Neck Bone Mass	Markedly Reduced
Bone Alkaline Phosphatase	Persistently Low
Vitamin B6 Levels	Normal
Total Fat Mass	~2nd Percentile

Key Findings

The patient has a homozygous SFRP4 variant consistent with Pyle disease.
Severe and persistent bone pain was reported, impacting daily activities.
Bone imaging revealed cortical bone loss and diffuse bone marrow edema.
Low bone alkaline phosphatase levels suggest impaired mineralization.
A heterozygous ALPL variant of uncertain significance was identified.

Clinical Implications

Clinicians should consider the potential for chronic pain in patients with Pyle disease and assess for coexisting metabolic conditions. Management should focus on pain relief and monitoring for skeletal complications.

Conclusion

This case highlights the complex interplay between structural and metabolic factors in chronic bone pain associated with SFRP4-related disorders, warranting further investigation into targeted therapeutic approaches.