Primary Hyperparathyroidism and Bone Jens Bollerslev Oslo University

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

PTH in Endocrinology Metabolic Supportive

Outline • PHPT and Bone Remodeling • Bone Turnover in PHPT • Bone Mass in PHPT • Fractures in PHPT • Conclusions

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

Bone Remodeling Endocr Rev 2011

Bone Remodeling

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

Reconstructed Trabecular Remodeling Eriksen, 1986 Mosekilde, 2007

3 d-Reconstructed Trabecular Remodeling Dempster et al, 2007

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 Expected % Osteodensitometry: Silverberg, JBMR, 1989 Mosekilde, Clin Endo 2007

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

BMD Z-scores in Lumbar Spine and Femoral Neck after 5 years * * P = 0. 024 * P = 0. 027 Lundstam, JCEM 2015

Risk of Fracture in PHPT Vestergård et al, 2002

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

Morphometric Vertebral Fractures in pm Women with Mild PHPT Vignali, JCEM 200

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

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

Prevalent Morphometric Fractures at baseline Lundstam, JCEM 2015

Prevalent and New Morphometric Fractures after 5 years Lundstam JCEM 2015

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

Randomized, controlled study of Vit D treatment before and after surgery • 44 pts with newly diagnosed PHPT • Randomized to 2800 IU vs placebo D 3 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

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

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!

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