Journal
BONE
Volume 146, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2021.115900
Keywords
Quantitative backscattered electron; microscopy; Bone mineralization density distribution; Teriparatide; Histomorphometry; FGF23
Categories
Funding
- Finnish Medical Foundation, Helsinki, Finland
- Sigrid Juselius Foundation
- Folkhalsan Foundation
- Academy of Finland
- Helsinki University Research Funds
- Swedish Research Council
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
- Stockholm County Council
- American Society of Nephrology
- Children's Discovery and Innovation Institute at the David Geffen School of Medicine
- National Institutes of Health [DK080984, DK098627]
- Austrian Social Health Insurance Fund (OEGK)
- Austrian Workers' Compensation Board (AUVA)
- Helsinki University
- Helsinki University Hospital through the Doctoral Programme in Clinical Research
- Orion Research Foundation
- Finnish ORL-HNS Foundation
- Paivikki and Sakari Sohlberg Foundation
- Finnish-Norwegian Medical Foundation
- Jalmari and Rauha Ahokas Foundation
- Juhani Aho Foundation
- Novo Nordisk Foundation
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Patients with WNT1 or PLS3 mutations show unique bone mineralization patterns, with teriparatide having little effect on their bone matrix mineralization or formation. Children exhibit preserved bone formation with heterogeneous mineralization, while adults show low bone turnover with homogenous mineral content.
Context: Patients with osteoporosis-associated WNT1 or PLS3 mutations have unique bone histomorphometric features and osteocyte-specific hormone expression patterns. Objective: To investigate the effects of WNT1 and PLS3 mutations on bone material properties. Design: Transiliac bone biopsies were evaluated by quantitative backscattered electron imaging, immunohistochemistry, and bone histomorphometry. Setting: Ambulatory patients. Patients: Three pediatric and eight adult patients with WNT1 or PLS3 mutations. Intervention: Bone mineralization density distribution and osteocyte protein expression was evaluated in 11 patients and repeated in six patients who underwent repeat biopsy after 24 months of teriparatide treatment. Main outcome measure: Bone mineralization density distribution and protein expression. Results: Children with WNT1 or PLS3 mutations had heterogeneous bone matrix mineralization, consistent with bone modeling during growth. Bone matrix mineralization was homogenous in adults and increased throughout the age spectrum. Teriparatide had very little effect on matrix mineralization or bone formation in patients with WNT1 or PLS3 mutations. However, teriparatide decreased trabecular osteocyte lacunae size and increased trabecular bone FGF23 expression. Conclusion: The contrast between preserved bone formation with heterogeneous mineralization in children and low bone turnover with homogenous bone mineral content in adults suggests that WNT1 and PLS3 have differential effects on bone modeling and remodeling. The lack of change in matrix mineralization in response to teriparatide, despite clear changes in osteocyte lacunae size and protein expression, suggests that altered WNT1 and PLS3 expression may interfere with coupling of osteocyte, osteoblast, and osteoclast function. Further studies are warranted to determine the mechanism of these changes.
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