Ana Monegal

Universitat de Barcelona

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Co-Authors

Núria Guañabens

Universitat de Barcelona

145

Pilar Peris

Universitat de Barcelona

142

Albert Parés

Universitat de Barcelona

Silvia Ruiz‐Gaspà

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Laia Gifre

Hospital Universitari Germans Trias i Pujol

ÁM

África Muxí

Universitat de Barcelona

Françesca Pons

Hospital Clínic de Barcelona

J Muñoz-Gómez

Hospital Clínic de Barcelona

LÁ

Luisa Álvarez

Albert Einstein College of Medicine

Josep L. Carrasco

Universitat de Barcelona

Cooperative Institutions

Universitat de Barcelona

158

Hospital Clínic de Barcelona

141

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

112

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

Instituto de Salud Carlos III

Centro de Investigación Biomédica en Red

Universitat Autònoma de Barcelona

Center for Rheumatology

Hospital Universitari de Vic

Fundació Clínic per a la Recerca Biomèdica

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THU0429 Clinical significance of increased serum levels of FGF23 in fibrous dysplasia

Annals of the Rheumatic Diseases (2017)

Helena Flórez Stanislava Mandelikova Xavier Filella Ana Monegal Núria Guañabens

Background

Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder, caused by missense mutations of the GNAS1 gene and is characterized by the development of fibro-osseous lesions that replace normal bone. FD can present with a broad spectrum of clinical manifestations, including the development of hypophosphatemic osteomalacia which is due to the production of the phosphaturic hormone fibroblast growth factor 23 (FGF-23) by the dysplastic bone tissue. Nevertheless, the prevalence of this clinical complication is not well known.

Objectives

To analyse the serum levels of FGF-23 in patients with FD and determine their relationship with the extension and activity of the disease, as well as with serum phosphate levels.

Methods

Twelve patients (7F:5M) with FD with a mean age of 50.67±16.4 years (24–79) were included. The clinical reports of the patients were reviewed, with special attention to the extension and activity of the disease, number and location of the affected bones, clinical complications and treatments received. Serum FGF-23 values were recorded in all subjects (determined by Immunotopics, CA, USA [measuring FGF23 C- terminal], normal value <130 RU/ml), as well as serum phosphate and calcium values, bone turnover markers and their evolution with treatment.

Results

Serum levels of FGF-23 were increased (>130 RU/ml) in 6/12 patients (50%). In patients with and without high FGF-23 levels the number of affected bones (2.2±2 vs. 1.9±1, respectively) and the skeletal locations of FD were similar as was the age in both groups of patients (48.2±14 vs. 53.2±19 years). In addition, FD disease activity and extension were similar in the two groups as were the bone turnover marker values (FAO, PINP and CTx). Strikingly, differences between serum phosphate values were not observed between the two groups (FGF23 >130: 3.9±0.9 mg/dl vs. FGF23 <130: 3.5±0.6 mg/dl). Indeed, none of the patients with high FGF-23 levels had low serum phosphate values. Following bisphosphonate (zoledronate) treatment, there were no significant changes in FGF-23 values. Nevertheless, an increase of 123% was found in one patient receiving denosumab, although hypophosphatemia was not associated.

Conclusions

Patients with FD frequently present elevated FGF-23 values with no effects on serum phosphate levels, thereby suggesting the presence of an alteration in processing this protein in the dysplastic bone tissue in this disease. The role of denosumab treatment in FD and its repercussion on FGF-23 levels need further study.

Disclosure of Interest

None declared

Osteomalacia

Bone remodeling

GNAS complex locus

10.1136/annrheumdis-2017-eular.5261

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Effect of complete spinal cord injury on bone turnover and bone mineral density evolution: a 1 year follow-up study

Bone Abstracts (2014)

Laia Gifre Joan Vidal Silvia Ruiz‐Gaspà E. Portell Ana Monegal

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Bone remodeling

10.1530/boneabs.3.pp371

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SAT0486 Reference Intervals for Bone Turnover Markers in Spanish Premenopausal Women

Annals of the Rheumatic Diseases (2014)

Núria Guañabens Xavier Filella Ana Monegal Carmen Gómez‐Vaquero M. Luisa Bonet

Background

Bone turnover markers (BTMs) are used in clinical practice for assessing patients with osteoporosis and their treatment. In Spain it is necessary to fine-tune the reference intervals, since they were established years ago in a low number of individuals.

Objectives

The aims of this study were to establish robust reference intervals for BTMs in healthy young premenopausal Spanish women and to investigate the factors influencing BTMs.

Methods

185 women aged 35 to 45 yrs. from 13 centres in Catalonia were recruited. Blood and second void urine samples were collected between 8 and 10 a.m. after an overnight fast. Serum PINP and βCTX were measured by two automated methods (Elecsys, Roche^a and IDS-ISYS, Immunodiagnostic Systems^b), bone ALP by ELISA (IDS, Vitro), osteocalcin by IRMA (Cis Bio) and urinary NTX by ELISA (Osteomark, Vitro). PTH and 25OHD levels were measured in all participants, who completed a questionnaire on lifestyle factors. A quantile regression was fit to estimate the 5%, 50% and 95% percentiles for the BMTs, and the Fisher9s exact test and non-parametric tests were used to assess the influence of factors on BTMs.

Results

The median (P5-P95) for BTMs were: Bone ALP 9.3 (6.0-13.8) ng/ml, PINP^a 35.9 (20.8-60.6) ng/ml, PINP^b 35.8 (20.8-64.9) ng/ml, NTX 32.7 (19.3-68.9) nM/mM, CTX^a 0.250 (0.137-0.480) ng/ml, CTX^b 0.246 (0.107-0.541), Osteocalcin 14.0 (8.0-23.0) ng/ml. Oral contraceptive pills (OCPs) were reported in 10.9% of participants, mean BMI was 23 and 60% had 25OHD levels lower than 20 ng/ml. Women on OCPs had lower PINP levels (p=0.007).25OHD levels didn9t influence BTMs, but low BMI was associated with higher levels of almost all BTMs.

Conclusions

In conclusion, robust reference intervals for BTMs in a southern European country are provided.

Acknowledgements

This study was funded by a research grant from de Societat Catalana de Reumatologia.

Disclosure of Interest

None declared

DOI

10.1136/annrheumdis-2014-eular.1755

Bone remodeling

10.1136/annrheumdis-2014-eular.1755

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Laboratory Investigations Immunocytochemical Evidence on the Effects of Glucocorticoids on Type I Collagen Synthesis in Human Osteoblastic Cells

Laura Álvarez‐Álvarez Ana Monegal Pilar Peris J. Riba G. Ercilla

The effects of glucocorticoids on DNA syn- thesis andcellular function were assessedin cultures of human osteoblastic cells by using indirect immunoper- oxidase staining with a type I antiprocollagen antibody andby measuring procollagen type I N andC propep- tides (PINP, PICP) in the culture medium by radiometric methods. Likewise, we analyzed the correlation between intracellular immunostaining andprocollagen propep- tides released into the culture medium, as well as the correlation between PINP andPICP. Human osteoblasts were cultured with and without addition of dexametha- sone (DEX) at two supraphysiological concentrations, 10 )6 M and10 )7 M, for 24 and48 h. Treatment with DEX at 10 )6 M was associatedwith a significant d e- crease in the percentage of cells showing intracellular type I procollagen immunoreactivity at 24 and48 h ( P < 0.05). Similar effects were observedwith 10 )7 M DEX. Dexamethasone 10 )6 Ma nd 10 )7 M also induced sig- nificant decreases in PINP and PICP values after 24 and 48 h of treatment (P < 0.05). The decrease in in- tracellular procollagen immunoreactivity andpropeptide secretion was not associatedwith a red uction in DNA synthesis. A highly significant correlation was observed between the values of PINP andPICP in the culture medium as well as between the values of intracellular immunostaining andPINP andPICP ( P < 0.001). In conclusion, our results suggest that supraphysiological doses of glucocorticoids produce a direct inhibition on osteoblastic function through their effect on type I pro- collagen synthesis. Immunoperoxidase detection of type I intracellular procollagen as well as the quantification of PINP andPICP in the culture med ium are reliable methods of assessing osteoblast function.

Procollagen peptidase

Immunostaining

Immunoperoxidase

Type I collagen

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Components of biological variation of biochemical markers of bone turnover in Paget’s bone disease

Bone (2000)

Laura Álvarez‐Álvarez Carmen Ricós Pilar Peris Núria Guañabens Ana Monegal

N-terminal telopeptide

Bone remodeling

Hydroxyproline

Type I collagen

10.1016/s8756-3282(00)00279-9

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Citations (70)

Effects of bilirubin and sera from jaundiced patients on osteoblasts: Contribution to the development of osteoporosis in liver diseases

Hepatology (2010)

Silvia Ruiz‐Gaspà À. Martínez-Ferrer Núria Guañabens Marta Dubreuil Pilar Peris

Abstract Low bone formation is considered to be the main feature in osteoporosis associated with cholestatic and end-stage liver diseases, although the consequences of retained substances in chronic cholestasis on bone cells have scarcely been studied. Therefore, we analyzed the effects of bilirubin and serum from jaundiced patients on viability, differentiation, mineralization, and gene expression in the cells involved in bone formation. The experiments were performed in human primary osteoblasts and SAOS-2 human osteosarcoma cells. Unconjugated bilirubin or serum from jaundiced patients resulted in a dose-dependent decrease in osteoblast viability. Concentrations of bilirubin or jaundiced serum without effects on cell survival significantly diminished osteoblast differentiation. Mineralization was significantly reduced by exposure to 50 μM bilirubin at all time points (from −32% to −55%) and jaundiced sera resulted in a significant decrease on cell mineralization as well. Furthermore, bilirubin down-regulated RUNX2 (runt-related transcription factor 2) gene expression, a basic osteogenic factor involved in osteoblast differentiation, and serum from jaundiced patients significantly up-regulated the RANKL/OPG (receptor activator of nuclear factor-κB ligand/osteoprotegerin) gene expression ratio, a system closely involved in osteoblast-induced osteoclastogenesis. Conclusion: Besides decreased cell viability, unconjugated bilirubin and serum from jaundiced patients led to defective consequences on osteoblasts. Moreover, jaundiced serum up-regulates the system involved in osteoblast-induced osteoclastogenesis. These results support the deleterious consequences of increased bilirubin in advanced chronic cholestasis and in end-stage liver diseases, resulting in disturbed bone formation related to osteoblast dysfunction. (Hepatology 2011)

RUNX2

Viability assay

10.1002/hep.24605

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Citations (67)

Reference intervals for bone turnover markers in Spanish premenopausal women

Bone Abstracts (2014)

Núria Guañabens Xavier Filella Ana Monegal Carmen Gómez‐Vaquero M. Luisa Bonet

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Turnover Intention

Bone remodeling

10.1530/boneabs.3.pp237

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Citations (5)

THU0476 Spontaneous vertebral fracturesafter denosumab discontinuation: a report of 6 cases

Annals of the Rheumatic Diseases (2018)

Helena Flórez J. Ramírez Ana Monegal Núria Guañabens Pilar Peris

Background

Denosumab (Dmab) is an antiresorptive treatment with demonstrated efficacy in osteoporosis. However, discontinuation of Dmab has been associated with rapid bone loss, and recently, the development of vertebral fractures (VF) in some patients. It is essential to identify the risk factors for these adverse events and follow its evolution.

Objectives

To analyse the clinical characteristics, parameters of bone metabolism and evolution of patients developing VF after Dmab discontinuation.

Methods

Six women with spontaneous VF after Dmab discontinuation were included (median age 66 years^56–75). The clinical history, cause of osteoporosis, treatments received, fractures, Dmab treatment duration and discontinuation period were reviewed. Additionally, the clinical and densitometric evolution, and bone mineral parameters were also analysed after Dmab discontinuation.

Results

All the patients had postmenopausal osteoporosis, and one was receiving glucocorticoid treatment; 3/6 patients had previous fractures (2 VF and 1 calcaneus); 4/6 had previously received antiosteoporotic treatment (hormone replacement therapy, risedronate, alendronate, zoledronate [once or consecutively)] during 1–23 years. All had received Dmab for 24–53 months (median 37). The reasons for treatment discontinuation were: dental indication (1 patient), BMD improvement (T-score −1.2) (1 patient), poor adherence,¹ prescription problems and/or delay in administration.³ The median bone mineral density T-scores prior to VF were −2.6 (-1.2/–4) at the lumbar spine and −3.0 (-0.6/–3.7) at the femoral neck. The mean time between the last Dmab dose and VF was 9.5 months,^8–20 with a median of 5 VFs/patient.^2–8 No patient showed 25-OH vitamin D<20 ng/ml. After Dmab discontinuation, bone turnover markers increased (median increase +364% in PINP and +287% in NTx); one patient presented hypercalcaemia (Ca 11.3 mg/dL); and BMD decreased 1%–21% in the lumbar spine and 2%–6% in total hip at 8–19 months. After VF, 3 patients restarted Dmab, 1 received zoledronate and 2 alendronate. No new fractures occurred during follow-up.

Conclusions

Discontinuation of Dmab is associated with an increase in bone turnover markers and bone loss which can be associated with the development of spontaneous VF. Previous bisphosphonate therapy does not seem to decrease this risk. Further studies are needed to assess the optimal antiresorptive treatment and its duration after Dmab discontinuation.