1. Primary Hyperparathyroidism and Bone
Jens Bollerslev
Oslo University Hospital and University in Oslo, Norway

2. PTH in Endocrinology
Metabolic
Supportive

3. Outline PHPT and Bone Remodeling Bone Turnover in PHPT
Bone Mass in PHPT
Fractures in PHPT
Conclusions

4. Bone Growth and Renewal
Modeling during growth
Trabecular and Cortical remodeling in adulthood
Stochastic - dedicated to calcium homeostasis
- under hormonal control
Targeted - removal of micro-damage
- essential for mechanical properties
Parfitt 2002

5. Bone Remodeling
Endocr Rev 2011

6. Bone Remodeling

7. PTH: Regulation of Bone Cell Differentiation
Baron & Hesse, JCEM 2012

8. Reconstructed Trabecular Remodeling
Eriksen, 1986
Mosekilde, 2007

9. 3d-Reconstructed Trabecular Remodeling
Dempster et al, 2007

10. Bone Metabolism in PHPT
Biochemical: High turn-over; reversible bone loss
Histomorphometry:
Trabecular Bone Volume is maintained
Trabecularization of Endocortical Envelope
Cortical bone mass decreased
Osteodensitometry:
qBEI: quantitative Backscattered Electron Imaging
Expected %
Silverberg, JBMR, 1989
Mosekilde, Clin Endo2007

11. Bone Mineral Density in the Spine, Fem
Bone Mineral Density in the Spine, Fem. Neck and Proximal Radius at baseline and follow-up
N = 175; 115, and 95 respectively
JCEM, 2009
Bollerslev, JCEM, 2007/09

12. BMD Z-scores in Lumbar Spine and Femoral Neck after 5 years* *
P = 0.024 *
P = 0.024
P = 0.027
Lundstam, JCEM 2015

13. Risk of Fracture in PHPT
Vestergård et al, 2002

14. Risk of Fractures in PHPT in relation to operation
Berkson’s Bias: The risk of being diagnosed with a diagnosis of PHPT would be more likely in patients who had a Fracture event than in controls, who are not submitted to a systematic plasma calcium screening
Mollerup et al, 2002

15. Morphometric Vertebral Fractures in pm Women with Mild PHPT
Vignali, JCEM 2009

16. Morphometric Vertebral Fractures in pm Women with Mild PHPT
Vignali, JCEM 2009

17. Treatment options in mild PHPT
Observation
Surgery, the only curative treatment
Vitamin D
Treatment of Symptoms
Calcimimetics
Anti-osteoporotic drugs
Bisphosphonates
Estrogens/SERM’s

18. Prevalent Morphometric Fractures at baseline
Lundstam, JCEM 2015

19. Prevalent and New Morphometric Fractures after 5 years
Lundstam JCEM 2015

20. Meta-analysis of Skeletal Effects of Intervention in mild PHPT
Sankaran et al, JCEM 2010

21. Randomized, controlled study of Vit D treatment before and after surgery
44 pts with newly diagnosed PHPT
Randomized to 2800 IU vs placebo D3 daily for 26 wks before and after PTX
BMD increased in LS by 2.4% prior to surgery (Vit D vs placebo)
Rolighed, JCEM 2014

22. Randomized, controlled study of Vit D treatment before and after surgery
Rolighed, JCEM 2014

23. Primary Hyperparathyroidism and Bone
Conclusions: Bone turn-over is increased in PHPT Trabecular Bone seems to be preserved Cortical Bone loss – Trabecularization Increased Fracture Rate - even in asymptomatic, mild PHPT Surgery is curative – anti-resorptive as effective Vitamin D is of importance!

25. Bone Remodeling - Compartments
Hauge et al, 2001;
Andersen et al, 2009