title: Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5.
abstract: Patients with an activation mutation of the Lrp5 gene exhibit high bone mass (HBM). Limited information is available regarding compartment-specific changes in bone. The relationship between the phenotype and serum serotonin is not well documented. To evaluate bone, serotonin, and bone turnover markers (BTM) in Lrp5-HBM patients, we studied 19 Lrp5-HBM patients (T253I) and 19 age- and sex-matched controls. DXA and HR-pQCT were used to assess BMD and bone structure. Serum serotonin, sclerostin, dickkopf-related protein 1 (DKK1), and BTM were evaluated. Z-scores for the forearm, total hip, lumbar spine, forearm, and whole body were significantly increased (mean ± SD) between 4.94 ± 1.45 and 7.52 ± 1.99 in cases versus -0.19 ± 1.19 to 0.58 ± 0.84 in controls. Tibial and radial cortical areas, thicknesses, and BMD were significantly higher in cases. In cases, BMD at the lumbar spine and forearm and cortical thickness were positively associated and trabecular area negatively associated with age (r = 0.49, 0.57, 0.74, and -0.61, respectively, p < .05). Serotonin was lowest in cases (69.5 [29.9-110.4] ng/mL versus 119.4 [62.3-231.0] ng/mL, p < .001) and inversely associated with tibial cortical density (r = -0.49, p < .05) and directly with osteocalcin (OC), bone-specific alkaline phosphatase (B-ALP), and procollagen type 1 amino-terminal propeptide (PINP) (r = 0.52-0.65, p < .05) in controls only. OC and S-CTX were lower and sclerostin higher in cases, whereas B-ALP, PINP, tartrate-resistant acid phosphatase (TRAP), and dickkopf-related protein 1 (DKK1) were similar in cases and controls. In conclusion, increased bone mass in Lrp5-HBM patients seems to be caused primarily by changes in trabecular and cortical bone mass and structure. The phenotype appeared to progress with age, but BTM did not suggest increased bone formation.
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark. frostnielsen@yahoo.com
authors.forename: Morten
authors.initials: M
authors.lastname: Frost
authors.forename: Tom
authors.initials: T
authors.lastname: Andersen
authors.forename: Fatma
authors.initials: F
authors.lastname: Gossiel
authors.forename: Stinus
authors.initials: S
authors.lastname: Hansen
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
authors.forename: Wim
authors.initials: W
authors.lastname: van Hul
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
mesh_terms: D015502:Absorptiometry, Photon; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000375:Aging / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009929:Organ Size; D010641:Phenotype; D012701:Serotonin / Q000097:blood*; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C422903:SOST protein, human; D012701:Serotonin