Gustavo Duque

McGill University | McGill · Department of Medicine

The mechanisms involved in the anabolic effect of interferon gamma (IFNc) on bone have not been carefully examined. Using microarray expression analysis, we found that IFNc upregulates a set of genes associated with a tryptophan degradation pathway, known as the kynurenine pathway, in osteogenic differentiating human mesenchymal stem cells (hMSC)....

Muscle and bone are in constant interaction. With aging, there is a progressive decline in muscle mass, known as sarcopenia, as well as in bone mass, which is known as osteopenia/osteoporosis. Sarcopenia and osteoporosis increase the risk of suffering falls and fractures, respectively. In fact, the simultaneous occurrence of osteoporosis and sarcop...

Changes in the expression of lamin A/C, a fibrilar protein of the nuclear envelope, are associated with the cellular features of age-related bone loss. Reduced expression of lamin A/C inhibits osteoblastogenesis while facilitating adipogenic differentiation of mesenchymal stem cells (MSC) in vitro and in vivo. In this study we investigated the regu...

INTRODUCTION: Sarcopenia and osteopenia are two components of the frailty syndrome that could share common underlying mechanisms. Recently, we have reported that lamin A/C deficient mice (Lmna−/−) show both osteo and sarcopenia together with fat infiltration of muscle and bone (Tong et al, Mech Ageing and Develop, 2011). This evidence suggests that...

Lipotoxicity is an overload of lipids in non-adipose tissues that affects function and induces cell death. Lipotoxicity has been demonstrated in bone cells in vitro using osteoblasts and adipocytes in coculture. In this condition, lipotoxicity was induced by high levels of saturated fatty acids (mostly palmitate) secreted by cultured adipocytes act...

The biological aging of stem cells (exhaustion) is proposed to contribute to the development of a variety of age-related conditions. Despite this, little is understood about the specific mechanisms which drive this process. In this study, we assess the transcriptomic and proteomic changes in three different populations of mesenchymal progenitor cel...

Importance: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. Objective: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. Design: The GLIS...

Purpose of Review The objective of this review is to summarize the literature on the prevalence and diagnosis of obesity and its metabolic profile, including bone metabolism, focusing on the main inflammatory and turnover bone mediators that better characterize metabolically healthy obesity phenotype, and to summarize the therapeutic interventions...

Treatment options for sarcopenia are currently limited, and primarily rely on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. We aim to investigate the relationship between nutrient intake and lean mass, function, and...

Treatment options for sarcopenia are currently limited, primarily relying on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. Our objective is to investigate the relationship between nutrient intake and lean mass, func...

Background Current evidence suggests an association between sarcopenia and multiple negative outcomes. Traditional methods to diagnose sarcopenia are based on dual‐energy X‐ray absorptiometry (DXA) and whole body magnetic resonance imaging. These tests are complicated, time‐consuming and expensive. We aim to bring a more accessible way to diagnose...

Background Current evidence suggests an association between sarcopenia and multiple negative outcomes. Traditional methods to diagnose sarcopenia are based on dual‐energy X‐ray absorptiometry (DXA) and whole body magnetic resonance imaging. These tests are complicated, time‐consuming and expensive. We aim to bring a more accessible way to diagnose...

The biological aging of mesenchymal stem cells is proposed to contribute to the development of a range of musculoskeletal and systemic diseases associated with older adults, such as osteoporosis, sarcopenia, and frailty. Despite this, little is understood about the specific mechanisms which drive this stem cell exhaustion, with most studies evaluat...

Background Sarcopenia is associated with multiple adverse outcomes. Traditional methods to determine low muscle mass for the diagnosis of sarcopenia are mainly based on dual‐energy X‐ray absorptiometry (DXA), whole‐body magnetic resonance imaging (MRI) and bioelectrical impedance analysis. These tests are not always available and are rather time co...

Often observed with aging, the loss of skeletal muscle (sarcopenia) and bone (osteoporosis) mass, strength, and quality, is associated with reduced physical function contributing to falls and fractures. Such events can lead to a loss of independence and poorer quality of life. Physical inactivity (mechanical unloading), especially in older adults,...

This review focuses on providing physicians with insights into the complex relationship between bone marrow adipose tissue (BMAT) and bone health, in the context of weight loss through caloric restriction or metabolic and bariatric surgery (MBS), in people living with obesity (PwO). We summarize the complex relationship between BMAT and bone health...

Dual‐energy X‐ray absorptiometry (DXA) scans are one of the most frequently used imaging techniques for calculating bone mineral density, yet calculating fracture risk using DXA image features is rarely performed. The objective of this study was to combine deep neural networks, together with DXA images and patient clinical information, to evaluate...

Sarcopenia typically presents in people older than 65 years with signs and symptoms of low muscle strength and low physical performance, such as falls, feeling weak, walking slowly, difficulty rising from a chair, and loss of weight and muscle mass. The five-item SARC-F patient questionnaire and assessing gait speed are recommended for screening p...

Advancing age is associated with body composition changes that impact the health status and overall wellbeing of older adults. Muscle mass decreases, contributing to the loss of strength and physical function, a condition known as sarcopenia. Declining bone mineral density leads to osteopenia or osteoporosis, with an increased risk of fractures. Ad...

Introduction Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia’s Home Medicine Review (HMR) ca...

Background Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). This population has a solid potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications. H...

Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association betw...

Doctor Gustavo Duque, a geriatrician investigator, Professor Faculty of Medicine, Doctor Joseph Kaufman chair in geriatric medicine at McGill University and member of the steering committee of the Global Frailty Network, interviewed Doctor Emanuele Marzetti during the International Conference on Frailty and Sarcopenia Research 2023 in Toulouse, Fra...

We examined if an interaction exists between bone and muscle in predicting fractures in older men. Prospective data from the Osteoporotic Fractures in Men study was used to build Cox proportional hazards models. Predictors included HR-pQCT total volumetric BMD (Tt.BMD), trabecular BMD (Tb.BMD), cortical BMD (Ct.BMD) and cortical area (Ct.Ar) at dis...

Objective: Age-related declines in muscle and bone, alongside a shift towards greater adiposity, contribute to falls and fracture risk. Testosterone is osteogenic, myogenic, and catabolic to fat. As such, we examined the effects of testosterone therapy on musculoskeletal health and clinical outcomes in men. Methods: Electronic databases (Medline...

Background: Different measures of muscle strength, physical performance and body size/composition are used in various sarcopenia definitions. This study investigated which baseline measures best predict incident mortality and falls, and prevalent slow walking speed in older women and men. Materials and methods: Data for 899 women (mean age±stand...

Introduction: Growth differentiation factor 15 (GDF-15) has been shown to be a metabolic and appetite regulator in diabetes mellitus (DM) and obesity. We aimed to investigate (i) the association between GDF-15 and DM with and without poor physical function independent of inflammation and (ii) the prediction model for poor physical function in pref...

Purpose: To compare the diagnostic value of relative sit-to-stand muscle power with grip strength or gait speed for identifying a history of recurrent falls and fractures in older adults. Methods: Data from an outpatient clinic included anthropometry (height/weight), bone density, 5 times sit-to-stand time (stopwatch and standardized chair), gri...

Immobilization leads to muscle wasting and insulin resistance, particularly during ageing. It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti‐osteoporosis treatment, might protect muscle wasting independent of ucOC. We hypothesize that the combination of ucOC and iba...

Background: The Exercise interveNtion outdoor proJect in the cOmmunitY (ENJOY) Seniors Exercise Park program uses specialized outdoor equipment and a physical activity program to engage older people in physical activity, with multiple health benefits. We determined the cost-effectiveness of the ENJOY program. Methods: The economic evaluation com...

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), suggesting a close association between vitamin D and LTL. In this study, we examined the relationship between vitamin D...

Osteosarcopenia is a complex geriatric syndrome characterized by the presence of both sarcopenia and osteopenia/osteoporosis. This condition increases rates of disability, falls, fractures, mortality and mobility impairments in older adults. The purpose of this study was to analyze the Fourier Transform Infrared (FTIR) spectroscopy diagnostic power...

Background: Although it is well-admitted that cardiovascular health affects cognition, the association between orthostatic hypotension (OH) and cognition remains unclear. The objectives of the present study were i) to determine among the EPIDOS cohort (EPIdémiologie de l'OStéoporose) whether OH was cross-sectionally associated with cognitive impai...

Sarcopenia and osteoporosis are highly prevalent syndromes in older people, characterized by loss of muscle and bone tissue, and related to adverse outcomes. Previous reports indicate mid‐thigh DXA is well‐suited for the simultaneous assessment of bone, muscle, and fat mass in a single scan. Using cross‐sectional clinical data and whole‐body DXA im...

Objective To identify the obesity diagnosis with the highest association with physical frailty associated with sarcopenia EWGSOP II (sarcopenic obesity). Subjects and methods We performed a cross-sectional analysis of 371 community-dwelling older adults. Appendicular skeletal lean mass and total body fat (TBF) were assessed using dual-energy x-ray...

Background/objective: By having a better understanding of transitions in osteosarcopenia, interventions to reduce morbidity and mortality can be better targeted. The aim of this study was to show the rationale and method of using minimal clinically important differences (MCID's) to classify transitions, and the effects of demographic variables on...

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), which suggests a close association. In this study, we examined the relationship between vitamin D levels and LTL in old...

Purpose of Review This review focuses on the recent findings regarding bone marrow adipose tissue (BMAT) concerning bone health. We summarize the variations in BMAT in relation to age, sex, and skeletal sites, and provide an update on noninvasive imaging techniques to quantify human BMAT. Next, we discuss the role of BMAT in patients with osteoporo...

Objectives: To develop guidelines, informed by health-care consumer values and preferences, for sarcopenia prevention, assessment and management for use by clinicians and researchers in Australia and New Zealand. Methods: A three-phase Consumer Expert Delphi process was undertaken between July 2020 and August 2021. Consumer experts included adul...

To determine urban–rural differences influencing mortality in patients with hip fracture in Colombian Andes Mountains over a 1-year period. Purpose To identify the urban–rural differences of sociodemographic variables, fracture-related characteristics, and preoperative and postoperative clinical factors associated with 1-year mortality in patients...

Natural bioactive compound, Ursolic acid (UA), plus different types of exercise may exert the action on glycemic control, leading to clinical benefits in the prevention and treatment of aging/diabetes-associated complications. So, this study examined the effects of eight weeks combination of 250 mg of UA per day per kilogram of body weight of rat a...

Low handgrip strength, a hallmark measure of whole-body strength, has been linked with greater odds of cognitive decline and dementia; however, conflicting findings, which could be due to population characteristics and choice of tools, such for the assessment of handgrip strength and cognitive function domains, also exist. Therefore, we examined th...

Methods The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a...

Purpose: To determine whether osteosarcopenia is associated with a greater likelihood of recurrent fractures, as well as type of fracture, than osteopenia/osteoporosis or sarcopenia alone. Methods: Anthropometry (height/weight; scales and stadiometer), body composition (bone mineral density [BMD] and appendicular lean mass; dual-energy x-ray absor...

The use of cannabinoids as therapeutic drugs has increased among aging populations recently. Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, a...

Background Sarcopenia is an age‐associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia...

Hyperhomocysteinemia induces oxidative stress and chronic inflammation (both of which are catabolic to bone and muscle); thus, we examined the association between homocysteine and body composition and physical function in middle-aged and older adults. Data from the National Health and Nutrition Examination Survey was used to build regression models...

Circulating osteoprogenitors (COP) is a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). While there is functional overlap, it is not known how COP cells are related to bone marrow (BM)-derived MSCs (BM-MSCs) and other better characterized stromal progeni...

Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). These cells can differentiate into adipocyte, chondrocyte, myocyte, and osteoblast lineages. Considering that COP cells are isolated from peripheral blood, this popu...

Background our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. Methods Design systematic review and meta-analysis. Data sources Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. Eligibility criteria randomised controlled trials of older partici...

Background: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. Objectives: to create a set of evi...

Bone and muscle are closely linked mechanically and biochemically. Bone hormones secreted during bone remodeling might be linked to muscle mass and strength maintenance. Exercise elicits high mechanical strain and is essential for bone health. However, the relationship between commonly used bone turnover markers (BTMs) and muscle function in commun...

Background Older adults experience considerable muscle and bone loss that are closely interconnected. The efficacy of progressive resistance training programs to concurrently reverse/slow the age-related decline in muscle strength and bone mineral density (BMD) in older adults remains unclear. Objectives We aimed to quantify concomitant changes in...

It is now more than 2 years since the beginning of the COVID-19 pandemic, which has affected people around the globe, particularly older persons, who are at the highest risk of severe disease. In addition, many of those who survive will have symptoms that persist after the initial infection. COVID-19 infection severely affects function and mobility...

Background Preclinical studies have shown a therapeutic role of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1) inhibition with rapamycin and its analogues (rapalogues) on several age-related musculoskeletal disorders (MSKD). However, the applicability to humans of these findings is unknown. Objective To assess the efficacy of rap...

Osteosarcopenia is an age-related condition characterized by fragile bone and low muscle mass and function. Fat infiltration concomitantly contributes to age-related bone and muscle decline. Fat-secreted factors could be locally secreted in the muscle and bone marrow milieu affecting cell function and survival. However, the specific fat-related sec...

This study identified the costs and health-related quality of life impacts of several post-fracture multidisciplinary care pathways specific to individual skeletal site (hip, distal forearm, vertebrae, humerus). These care pathways may assist healthcare providers in allocating resources for osteoporotic fractures in more effective and cost-efficien...

Introduction Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with SARS-CoV-2 (COVID-19), which disproportionately impact older adults, particularly those in residential aged care facilities. Inadeq...

Purpose Two mechanisms implicated in telomere shortening are oxidative stress and inflammation, both of which are linked to bone and muscle loss suggesting a pathological link between telomere attrition and osteosarcopenia. Using older adults aged 60 years and over in the UK Biobank, we examined the association between leukocyte telomere length and...

General muscle health declines with age, and in particular, sarcopenia—defined as progressive loss of muscle mass and strength/physical performance—is a growing issue in Asia with a rising population of community‐dwelling older adults. Several guidelines have addressed early identification of sarcopenia and management, and although nutrition is cen...

Accurate quantification of bone, muscle, and their components is still an unmet need in the musculoskeletal field. Current methods to quantify tissue volumes in 3D images are expensive, labor-intensive, and time-consuming; thus, a reliable, valid, and quick application is highly needed. Tissue Compass is a standalone software for semiautomatic segm...

Background : Age-related neurodegeneration, sarcopenia, and ectopic fat accumulation are conditions with shared pathways that remain poorly understood. We have measured muscle volume and fat accumulation in masseter and tongue muscle, and aim to explore their association with the total grey matter volume using MRI in older adults recently diagnosed...

Frailty is defined as a syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes. A robust biomarker for frailty is still lacking. Tryptophan (TRP) metabolism through the kynurenine pathway (KP) plays essential roles in aging, the musculoskeletal system, and physical performance. In this study...

Background Falls in older persons are associated with muscle mass and strength alterations, which may also affect balance parameters. However, the most appropriate combined approach to assess muscle and balance components that predict falls in older persons is still lacking. Research question We hypothesized that appendicular lean and/or mid-thigh...

Background It is not known how measures of body composition, strength and physical performance are interrelated or how empirical groupings of these measures relate to disability and mobility disability. Methods Muscle mass was assessed by D3-creatine dilution (D3Cr muscle mass) in 1345 men (84.1 ± 4.1 years) enrolled in the Osteoporotic Fractures...

Introduction Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with Sars-Cov2, which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrien...

Osteoporosis is underdiagnosed and undertreated in people living in Residential Aged Care Facilities (RACFs), even though aged-care residents are at greater risk of experiencing fractures than their community-dwelling counterparts. The first (2009) and second (2016) Consensus Conferences on the Treatment of Osteoporosis in RACFs in Australia addres...

The active form of vitamin D (1, Alpha 25-Hydroxyvitamin D 3 ; [1α,25(OH) 2 D 3 ]) is associated with multiple cellular processes, including bone formation. Severe vitamin D deficiency (as defined by serum 25-Hydroxyvitamin D <30nmol/L) typically results in growth retardation, rickets and osteomalacia. Conversely, 1α,25-(OH) 2 D 3 treatment demonst...

Background Markers of bone metabolism have been associated with muscle mass and function. Whether serum cross-linked C-terminal telopeptides of type I collagen (CTX) is also associated with these measures in older adults remains unknown. Methods In community-dwelling older adults at high risk of falls and fractures, serum CTX (biochemical immunoas...

Background The ENJOY project (Exercise interveNtion outdoor proJect in the cOmmunitY for older people) is a community-based research project actively promoting physical activity engagement through the delivery of an exercise program using outdoor multimodal exercise equipment. This study investigated the impact of the physical activity program on f...

Osteosarcopenia is a growing healthcare challenge. This is compounded by a lack of pharmacological strategies to treat both muscle and bone simultaneously. While there are no approved medications for osteosarcopenia, there are some compounds that are known to have a dual role in the treatment of muscle and bone. This chapter discusses the relevant...

The global population is aging as a result of improved overall health care and socioeconomic standards of living. The frequency of falls and risk of falls-related injury increases with age. Falls are a major cause of morbidity and mortality worldwide. Despite this, falls should not be viewed as an inevitable part of aging. Identifying modifiable fa...

COP cells have been identified as having a potential role in the pathogenesis of tissue loss syndromes such as osteoporosis and frailty. This is based on the hypothesis that their dysregulation may cause a decrease in bone and muscle formation, which also increase the risk of adverse outcomes such as frailty and disability. Whereas high numbers of...

Circulating osteogenic progenitor (COP) cells are a population of cells in the peripheral blood with the capacity for bone formation and broader differentiation into mesoderm-like cells in vitro. While some of their biological characteristics are documented in vitro, their role in the aging process and the pathogenesis of musculoskeletal diseases r...

Background The ratio of creatinine to cystatin C (Cr:Cyc) has been proposed as a biomarker of sarcopenia, as greater Cr:Cyc is typically associated with greater muscle mass. We examined the relationship between Cr:Cyc with individual sarcopenia measures, 5 y self-reported falls and 12 y fall-related hospitalizations in a prospective cohort study of...

Background: Circulating osteoprogenitor (COP) cells are a surrogate of the bone marrow mesenchymal stem cells with high levels observed in osteoporosis and the initial stages of fracture healing. Conversely, a low percentage of COP cells (%COP) is strongly associated with frailty and disability. However, it is unknown whether %COP is associated wi...

Little is known about factors that lead to excess mortality post-fracture. This study demonstrated that 5-year mortality is lower in older adults who recovered to their pre-fracture health-related quality of life (HRQoL) at 12-months compared to those who did not recover. Our results highlight the importance of post-fracture interventions known to...

Osteoporosis is a condition of growing concern in all areas of healthcare, with osteopathic practice no exception. Allied health clinicians and other manual/physical practitioners are well placed to play a role in prevention, early detection and intervention in these patients, as well as in ongoing fall and fracture prevention. This masterclass aim...

Background Falls are a significant cause of injuries, loss of confidence, increased morbidity, and institutionalisation in all older people, with women at 50% greater risk than men. The relationship between dementia and falls is well established and 2/3 of all dementia occurs in women. In this study we explored risk factors associated with a 14 yea...

Background Osteoglycin (OGN) is a proteoglycan released from bone and muscle, which has been associated with markers of metabolic health. However, it is not clear whether the levels of circulating OGN change throughout the adult lifespan or if they are associated with clinical metabolic markers or fitness. Methods 107 individuals (46 males and 61...

Background: Aging results in musculoskeletal disorders, which are a leading cause of disability worldwide. While conventional nonpharmacological treatments have included interventions such as resistance exercise, there are subgroups of people who may be at risk of exercise-related injuries, for example, falls. Whole-body vibration (WBV) is an inte...

To examine the prevalence of sarcopenia and its association with antirheumatic drugs in adults with rheumatoid arthritis (RA). This review was registered on PROSPERO and followed PRISMA guidelines. Electronic databases were searched for studies reporting on the prevalence of sarcopenia in adults with RA using any muscle index (muscle mass, strength...

Introduction/Objectives High serum concentrations of parathyroid hormone (PTH) have been associated with osteoporosis, sarcopenia and osteosarcopenia. Gait velocity is a predictor of adverse outcomes. This systematic review aimed to assess the observational evidence studying the association of PTH concentrations with gait velocity in adults. Metho...

ABSTRACT Circulating osteo progenitor (COP) cells are a heterogeneous population of cells that circulate within the peripheral blood with characteristics of the bone marrow mesenchymal stem and progenitor pool. Little is known about the behavior of this cell population in humans. The aim of this study was to identify whether a relationship exists b...

Background: Sarcopenia is associated with significant morbidity and mortality in patients with chronic kidney disease. The prevalence of sarcopenia in the dialysis population varies from 4% to 63%. However, the prevalence and risk factors of sarcopenia in the Australian dialysis population remain uncertain. Aim: To study the prevalence of sarcopeni...

Background Increasing protein intake (above the Recommended Dietary Amount) alone or with resistance‐based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. Methods The Liverpool Hope University‐Sarcopenia Aging Trial (LHU‐SAT) was a 16 week RCT (ClinicalTrials.gov Ide...

Picolinic acid (PIC) is a byproduct of tryptophan catabolism through the kynurenine pathway, with anabolic effects on bone in vivo and in vitro. Hence, PIC has been nominated as a possible candidate to treat and/or prevent osteoporosis. However, the effective dose and toxicity of PIC are not known yet. To test the effect of escalating and very high...