The role of carboxy-terminal cross-linking telopeptide of type I collagen, dual x-ray absorptiometry bone strain and Romberg test in a new osteoporotic fracture risk evaluation: A proposal from an observational study

PLOS ONE, Nov 2019

The consolidated way of diagnosing and treating osteoporosis in order to prevent fragility fractures has recently been questioned by some papers, which complained of overdiagnosis and consequent overtreatment of this pathology with underestimating other causes of the fragility fractures, like falls. A new clinical approach is proposed for identifying the subgroup of patients prone to fragility fractures. This retrospective observational study was conducted from January to June 2015 at the Nuclear Medicine-Bone Metabolic Unit of the of the Fondazione IRCCS Ca' Granda, Milan, Italy. An Italian population of 125 consecutive postmenopausal women was investigated for bone quantity and bone quality. Patients with neurological diseases regarding balance and vestibular dysfunction, sarcopenia, past or current history of diseases and use of drugs known to affect bone metabolism were excluded. Dual X-ray absorptiometry was used to assess bone quantity (bone mineral density) and bone quality (trabecular bone score and bone strain). Biochemical markers of bone turnover (type I collagen carboxy-terminal telopeptide, alkaline phosphatase, vitamin D) have been measured. Morphometric fractures have been searched by spine radiography. Balance was evaluated by the Romberg test. The data were evaluated with the neural network analysis using the Auto Contractive Map algorithm. The resulting semantic map shows the Minimal Spanning Tree and the Maximally Regular Graph of the interrelations between bone status parameters, balance conditions and fractures of the studied population. A low fracture risk seems to be related to a low carboxy-terminal cross-linking telopeptide of type I collagen level, whereas a positive Romberg test, together with compromised bone trabecular microarchitecture DXA parameters, appears to be strictly connected with fragility fractures. A simple assessment of the risk of fragility fracture is proposed in order to identify those frail patients at risk for osteoporotic fractures, who may have the best benefit from a pharmacological and physiotherapeutic approach.

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The role of carboxy-terminal cross-linking telopeptide of type I collagen, dual x-ray absorptiometry bone strain and Romberg test in a new osteoporotic fracture risk evaluation: A proposal from an observational study

January The role of carboxy-terminal cross-linking telopeptide of type I collagen, dual x-ray absorptiometry bone strain and Romberg test in a new osteoporotic fracture risk evaluation: A proposal from an observational study Fabio M. Ulivieri 0 2 3 Luca P. Piodi 0 1 3 Enzo Grossi 0 3 Luca Rinaudo 0 3 Carmelo Messina 0 3 Anna P. Tassi 0 3 Marcello Filopanti 0 3 Anna Tirelli 0 3 Francesco Sardanelli 0 3 0 Nuclear Medicine-Bone Metabolic Unit of the of the Fondazione IRCCS Ca' Granda , Milan 1 Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico , Milan , Italy , 3 Villa Santa Maria Institute , Tavernerio (CO), Italy, 4 TECHNOLOGIC S.r.l. Hologic Italia, Turin , Italy , 5 Postgraduation School in Radiodiagnostics, University of Milan , Milan , Italy , 6 Physical Medicine and Rehabilitation Physician, A.S.P. I.M.M e S. e P.A.T , Milan , Italy , 7 Endocrinology and Metabolic Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy , 8 Clinical Chemistry and Microbiology Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy , 9 Radiodiagnostics Unit, IRCCS Policlinico San Donato , Milan , Italy 2 Nuclear Medicine Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico , Milan , Italy 3 Editor: Chun Kee Chung, Seoul National University College of Medicine , REPUBLIC OF KOREA The consolidated way of diagnosing and treating osteoporosis in order to prevent fragility fractures has recently been questioned by some papers, which complained of overdiagnosis and consequent overtreatment of this pathology with underestimating other causes of the fragility fractures, like falls. A new clinical approach is proposed for identifying the subgroup of patients prone to fragility fractures. - Data Availability Statement: All relevant data are within the paper and its Supporting Information file. Funding: TECHNOLOGIC S.r.l provided support in the form of salary for author LR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of The data were evaluated with the neural network analysis using the Auto Contractive Map algorithm. The resulting semantic map shows the Minimal Spanning Tree and the Maximally Regular Graph of the interrelations between bone status parameters, balance conditions and fractures of the studied population. A low fracture risk seems to be related to a low carboxy-terminal cross-linking telopeptide of type I collagen level, whereas a positive Romberg this author are articulated in the `author contributions' section. Competing interests: We have disclosed the affiliation to TECHNOLOGIC S.r.l. in our Financial Disclosure statement and we have confirmed that this commercial affiliation does not alter our adherence to all PLOS ONE policies on sharing data and materials. test, together with compromised bone trabecular microarchitecture DXA parameters, appears to be strictly connected with fragility fractures. A simple assessment of the risk of fragility fracture is proposed in order to identify those frail patients at risk for osteoporotic fractures, who may have the best benefit from a pharmacological and physiotherapeutic approach. Introduction Osteoporosis (OP) is a pathological condition in which a reduction in bone mass and an impairment of microarchitecture are found. The consequence is a decrease in bone strength, which is the result of the sum of good bone quantity and quality, followed by an increase in bone fragility [ 1,2 ]. Fractures lead to high rates of disability and mortality with high social costs. It has been calculated that, among women's deaths associated with fractures, about 50% are due to hip fractures, 28% to vertebral fractures and 22% to fractures in other sites[1±4]. Moreover, vertebral fractures, which are the most frequent but less dangerous osteoporotic fractures, are directly related to a high risk of subsequent fractures[ 5,6 ]. Diagnosis of OP and follow-up of its treatment are performed by dual X-ray photon absorptiometry (DXA), measuring areal bone mineral density (aBMD), which is considered the most accurate diagnosing method, being aBMD the main parameter reflecting bone strength[ 7 ]. Following the indications of International Societies [ 8 ], the densitometric scans are obtained from lumbar spine and proximal femur, which are the bone segments more frequently affected by osteoporotic ªfragilityº fractures, that means occurring with minimal or no trauma at all. The drawn aBMD value is expressed as T-score (standard deviation from the normal reference population) and Z-score (standard deviation from the sex and age matched population). Recently, a new tool derived from DXA by a specific software has been developed, called trabecular bone score (TBS), which is able through a numerical value to give insight to the microarchitectura (...truncated)


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Fabio M. Ulivieri, Luca P. Piodi, Enzo Grossi, Luca Rinaudo, Carmelo Messina, Anna P. Tassi, Marcello Filopanti, Anna Tirelli, Francesco Sardanelli. The role of carboxy-terminal cross-linking telopeptide of type I collagen, dual x-ray absorptiometry bone strain and Romberg test in a new osteoporotic fracture risk evaluation: A proposal from an observational study, PLOS ONE, 2018, Volume 13, Issue 1, DOI: 10.1371/journal.pone.0190477