Persistent Reduction of Circulating Myeloid Calcifying Cells in Acromegaly: Relevance to the Bone-Vascular Axis.
Acromegaly is a systemic disease characterized by persistent bone pathology and excess cardiovascular mortality. Despite multiple concomitant risk factors, atherosclerosis does not seem to be accelerated in acromegaly.



To compare the levels of circulating myeloid calcifying cells (MCCs), which promote ectopic calcification and inhibit angiogenesis, in individuals with and without acromegaly.



Cross-sectional case-control study.



Tertiary ambulatory referral endocrinology center.



44 acromegalic patients (25 active; 19 inactive), 44 control subjects matched by age, sex, risk factors, and medications, and 8 patients cured of acromegaly.



MCCs were measured using flow cytometry based on the expression of osteocalcin (OC) and bone alkaline phosphatase (BAP) on monocytes and circulating CD34+ stem cells.



Differences in MCCs between patients and controls.



OC+BAP+ MCCs were severely reduced in acromegalic compared with control patients (0.17% ± 0.02% vs 1.00% ± 0.24%; P < 0.001), as were the total OC+ and BAP+ monocytic cells. Patients with inactive acromegaly and those cured of acromegaly displayed persistently reduced levels of MCCs. In the controls, but not acromegalic patients, MCCs were increased in the presence of diabetes or cardiovascular disease. A direct correlation was noted between MCCs and parathyroid hormone (r = 0.61; P < 0.0001), supporting a link between bone biology and MCCs.



In patients with acromegaly, the levels of MCCs are reduced and remain low, even years after a complete cure. This finding might be related to low atherosclerotic calcification and the persistence of bone pathology after acromegaly remission or cure.
Department of Medicine, University of Padua, Padua 35128, Italy.|Venetian Institute of Molecular Medicine, Padua 35128, Italy.
Gian Paolo
GP
Fadini
Department of Medicine, University of Padua, Padua 35128, Italy.
Francesca
F
Dassie
Department of Medicine, University of Padua, Padua 35128, Italy.
Roberta
R
Cappellari
Department of Medicine, University of Padua, Padua 35128, Italy.
Mariasara
M
Persano
Department of Medicine, University of Padua, Padua 35128, Italy.
Saula
S
Vigili de Kreutzenberg
Department of Medicine, University of Padua, Padua 35128, Italy.
Chiara
C
Martini
Department of Medicine, University of Padua, Padua 35128, Italy.
Matteo
M
Parolin
Department of Medicine, University of Padua, Padua 35128, Italy.
Angelo
A
Avogaro
Department of Medicine, University of Padua, Padua 35128, Italy.
Roberto
R
Vettor
Department of Medicine, University of Padua, Padua 35128, Italy.
Pietro
P
Maffei
D000236:Adenoma / Q000097:blood* / Q000188:drug therapy; D000469:Alkaline Phosphatase / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D002114:Calcinosis; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood* / Q000188:drug therapy; D019382:Human Growth Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D015675:Osteocalcin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D018952:Antigens, CD34; D018931:Antineoplastic Agents, Hormonal; D015675:Osteocalcin; D019382:Human Growth Hormone; D013004:Somatostatin; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; C406545:pegvisomant