Mh Lafage-Proust

• MD, PhD
• Senior Researcher at French Institute of Health and Medical Research

Background and Purpose: Bone metastases are frequent complications of breast cancer, facilitate the development of anarchic vascularization and induce bone destruction. Therefore, anti-angiogenic drugs (AAD) have been tested as a therapeutic strategy for the treatment of breast cancer bone metastasis. However, the kinetics of skeletal vascularizati...

Chronic kidney disease (CKD) induces mineral and bone disorders (CKD-MBD) that affect calcium and phosphate metabolism. This review links pathophysiology, histologic aspects, and radiologic signs. CKD leads to bone lesions, namely renal osteodystrophy, which may combine low or high bone remodeling, impaired mineralization, and bone loss. CKD-MBD al...

Impaired mechanical stimuli during hindlimb unloading (HLU) are believed to exacerbate osteocyte paracrine regulation of osteoclasts. We hypothesized that bone loss and deterioration of the osteocyte lacuno-canalicular network are attenuated in HLU mice housed at thermoneutrality (28 °C) compared with those housed at ambient temperature (22 °C). Fo...

The coexistence of osteoporosis and chronic kidney disease (CKD) is an evolving health care challenge in the face of increasingly aging populations. Globally, accelerating fracture incidence causes disability, impaired quality of life, and increased mortality. Consequently, several novel diagnostic and therapeutic tools have been introduced for tre...

Purpose: To evaluate whole-body vibration (WBV) osteogenic potential in physically inactive postmenopausal women using high-frequency and combined amplitude stimuli. Methods: Two-hundred fifty-five physically inactive postmenopausal women (55–75 years) with 10-year major osteoporotic fracture risk (3%–35%) participated in this 18-month study. For t...

Nacre has emerged as a beneficial natural product for bone cells and tissues, but its effect was only studied by gavage in the ovariectomized mouse model. We sought to assess the anti‐osteoporotic effect of nacre through a nutritional supplementation in the ovariectomized rat model. Sixteen‐week‐old female Wistar rats were either Sham‐operated or b...

Bone metastases are frequent complications of breast cancer, facilitating the development of anarchic vascularization and induce bone destruction. Therefore, anti-angiogenic drugs (AAD) have been tested as a therapeutic strategy for the treatment of breast cancer bone metastasis. However, the kinetics of skeletal vascularization in response to tumo...

A transiliac bone biopsy is recommended to help guide therapy of bone disease in chronic kidney disease. Due to a lack of consensus on normative references for bone histomorphometry, diagnostic cutoffs vary substantially, which may affect treatment advice. This cross-sectional, observational study investigates the impact of different diagnostic def...

X-linked hypophosphatemia (XLH) is a genetic disease mostly related to PHEX gene mutations which increases FGF23 serum levels, leading to hypophosphatemia and osteomalacia in adults, while affected children, in addition, develop rickets. Most of adults with XLH suffer from reduced quality of life and physical disability due to chronic bone and join...

Osteoarthritis (OA) is a whole joint disease characterized by an important remodeling of the osteochondral junction. It includes cartilage mineralization due to chondrocyte hypertrophic differentiation and bone sclerosis. Here, we investigated whether gremlin-1 (Grem-1) and its BMP partners could be involved in the remodeling events of the osteocho...

Introduction La morbidité du diabète est liée aux complications vasculaires que sont la macro- et la microangiopathie. De plus, les diabètes de type 1 (DT1) et 2 (DT2) augmentent le risque fracturaire. Or, la vascularisation osseuse joue un rôle majeur dans la physiologie du tissu osseux. Malgré le caractère multifactoriel de la fragilité osseuse d...

Introduction À cause des variations de fréquence(haute/basse), d’accélération (< 1/ > 1 g) et du temps d’exposition aux stimuli vibratoires, l’incertitude demeure quant à l’effet ostéogénique des vibrations corps entier (VCE)[1], [2]. L’efficacité des VCE dans une population de femmes ménopausées, a été étudiée avec deux objectifs : – analyser le p...

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the...

The European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4–5D (eGFR < 30 ml/min 1.73 m2)...

Chronic kidney disease is defined as a decrease in renal function or evidence of kidney injury for >3 months. This represents an oversimplification that may confuse physicians. Thus kidney function is equated to glomerular filtration rate, which represents one of multiple kidney functions. Some potentially more important renal functions are lost ea...

Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeletal system are limited. Our goal was to analyze musculoskeletal changes in OA mice and test the efficacy of 8-week exposure to hypergravity, as a replacement of physical activity. 16-week-old male (C57BL/6J) mice allocated to sham control and OA groups no...

Objectives We hypothesize that chondrocytes from the deepest articular cartilage layer are pivotal in maintaining cartilage integrity and that the modification of their prehypertrophic phenotype to a hypertrophic phenotype will drive cartilage degradation in osteoarthritis. Design Murine immature articular chondrocytes (iMACs) were successively cu...

Controlling the excessive fracture burden in patients with chronic kidney disease (CKD) Stages G4-G5D remains an impressive challenge. The reasons are 2-fold. First, the pathophysiology of bone fragility in patients with CKD G4-G5D is complex and multifaceted, comprising a mixture of age-related (primary male/postmenopausal), drug-induced and CKD-r...

Objective TGFβ is a key player in cartilage homeostasis and OA pathology. However, few data are available on the role of TGFβ signalling in the different OA phenotypes. Here, we analysed the TGFβ pathway by transcriptomic analysis in six mouse models of OA. Method We have brought together seven expert laboratories in OA pathophysiology and, used i...

Background and objectives Histomorphometric analysis of a transiliac bone biopsy is the gold standard for the diagnosis of renal osteodystrophy (ROD). This procedure is costly, invasive and usually performed with a trephine with an internal diameter of 7.5 mm. Our objective was to evaluate the accuracy of ROD diagnosis on halved histological bone s...

Introduction: Severe uncontrolled secondary hyperparathyroidism and kidney transplantation history are both risk factors for fractures in hemodialyzed patients. Moreover, patients who return to dialysis after transplant failure have more severe infections/anemia and higher mortality risk than transplant-naive patients starting dialysis with native...

Intermittent Parathyroid Hormone (iPTH) is anti‐osteoporotic and affects bone vessels. Transitional capillaries close to the bone surface, which express both endomucin (Edm) and CD31, bear Leptin receptor‐expressing (LepR) perivascular cells that may differentiate into osteoblasts. Increased numbers of type H endothelial cells (THEC, ie Edmhi/ CD31...

Osteogenesis imperfecta (OI) is a genetic disease whose clinical phenotype and severity vary considerably. The increased risk of fractures due to bone fragility persists in adulthood, notably after 40 years of age, albeit at a lower level than during growth. Adults with OI require periodic evaluations of the other manifestations of OI including hea...

The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts. In mature BSP knockout (KO, -/-) mice, both bone formation and resorption as well as mineralization are impaired. OPN-/- mice display impaired resorption, and OPN is described as an inhi...

Résumé L’ostéogénèse imparfaite (OI), est une maladie génétique dont la présentation clinique et la sévérité sont variables. À l’âge adulte, les patients atteints d’OI présentent une fragilité osseuse persistante qui augmente l’incidence des fractures, notamment après 40 ans, même si cette incidence est réduite par rapport à la période de croissanc...

All the functions of bone, including locomotion, hematopoiesis, calcium/phosphate metabolism, and endocrine secretions, depend on a common blood supply. Oxygen tension, which depends on bone perfusion, is a key regulatory factor in bone. MRI‐based studies showed reduced bone perfusion in postmenopausal osteoporotic women compared to age‐matched hea...

The effects of whole body vibration on musculoskeletal system might depend on the vibration regimen. In this study, a group of 100 sedentary postmenopausal women (55 to 75 years old) were subjected to whole body vibration (35-50 Hz frequency, 0.2-0.8 mm amplitude, 3 sessions/week) while they performed passive and active squat exercises for a period...

Background Secondary hyperparathyroidism (SHPT) is a frequent complication of renal disease and most commonly occurs in patients on haemodialysis (HD) with metabolic, vascular, endocrine, and bone complications. The aim of this study was to analyze the evolution of mineral metabolism parameters during the first 36 months of HD treatment and identif...

Chronic kidney disease (CKD) is a risk factor for fractures. The current evaluation of fracture risk is based upon the combination of various clinical factors and quantitative imaging of bone. X-ray-based tools were developed to evaluate bone status and predict fracture risk. Dual energy X-ray absorptiometry (DXA) is available worldwide. Longitudin...

Renal osteodystrophy (ROD) is a heterogeneous group of metabolic bone diseases complicating progressive chronic kidney disease (CKD). Bone biomarkers and bone imaging techniques may help to assess bone health and predict fractures in CKD but do have important inherent limitations. By informing on bone turnover and mineralization, a bone biopsy may...

The number of serum 25-hydroxyvitamin D (25OHD) assays has increased tenfold in France in less than 10 years, sometimes for invalidated reasons. In 2013, the French National Authority for Health (Haute autorité de santé, or HAS) limited the indications for serum 25OHD measurements to rickets/osteomalacia, older adults with recurrent falls, monitori...

Ossification is a key stage of bone development and growth. This complex process combines cell–cell contacts, cell proliferation and apoptosis, cell migration and differentiation, vasculogenesis, matrix synthesis, and mineralization. The complete ossification of the skeleton is a very long process that begins as early as the first weeks of fetal de...

The bone organ integrates the activity of bone tissue, bone marrow and blood vessels and the factors ensuring this coordination remain ill defined. Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the Small Integrin Binding Ligand N-Linked Glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis. In rod...

Bone Sialoprotein (BSP) is a member of the “Small Integrin-Binding Ligand N-linked Glycoproteins” (SIBLING) extracellular matrix protein family of mineralized tissues. BSP has been less studied than other SIBLING proteins such as Osteopontin (OPN), which is coexpressed with it in several skeletal cell types. Here we review the contribution of genet...

Ossification is a complex process which involves tightly regulated processes, the disorder of which leads to pathological growth. Here we summarize the local molecular mechanisms which control bone growth and development. Neither hormonal regulations nor effects of genetic mutations are addressed in this review.

One of the most important but least studied environmental factors playing a major role in bone physiology is gravity. While the knowledge of deleterious effects of microgravity on the skeleton is expanding, little is known about hypergravity and its osteogenic potential. Centrifugation was used to assess effects of 21-d continuous 2g or 3g accelera...

Metabolic and bone effects were investigated in growing (G, n = 45) and mature (M, n = 45) rats fed a high-fat-sucrose diet (HFS) isocaloric to the chow diet of controls (C, n = 30 per group). At week-19, a subset of 15 rats in each group (HFS or C, at both ages) was analyzed. Then half of the remaining 30 HFS rats in each groups continued HFS and...

Sclerostin is an osteocyte-specific glycoprotein secreted by the osteocyte and involved in the regulation of bone mass. High sclerostin levels are associated with osteoporosis, whereas low sclerostin levels are correlated with higher bone mineral density. It seems interesting to investigate a potential association between sclerostin levels and vasc...

We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently a...

Bone is a composite organ that fulfils several interconnected functions, which may conflict with each other in pathological conditions. Bone vascularization is at the interface between these functions. The roles of bone vascularization are better documented in bone development, growth and modeling than in bone remodeling. However, every bone remode...

Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1-84 (iPTH) over the calvaria of BSP knockout (-/-) mice to investigate further their functional specificity and redundancy.iPTH stimulated bone formation in both +/+ and -/...

A new definition and classification of chronic kidney disease-mineral and bone disorder (CKD-MBD) was proposed in 2005 and it was later followed by a guideline publication on this topic from Kidney Disease: Improving Global Outcomes (KDIGO) in 2009. This work recognized that CKD-MBD is a syndrome of bone abnormalities, laboratory abnormalities, and...

The periosteum covers most bone structures. It has an outer fibrous layer and an inner cambial layer that exhibits osteogenic activity. The periosteum is a dynamic structure that plays a major role in bone modeling and remodeling under normal conditions. In several disorders such as infections, benign and malignant tumors, and systemic diseases, th...

Background Bisphosphonates have been widely used for treatment of high bone resorption states. It lowers bone turnover by inhibiting osteoclasts bone resorption with various mechanisms of actions: inhibition of osteoclast formation and attachment to the bone surface, induction of metabolic injury, alteration of vesicle trafficking and induction of...

Bone vessels functions during bone remodeling are poorly understood. They depend on both vessel network structure and vasomotor regulation. Parathyroid hormone (PTH) is a systemic vasodilator and may modulate microvascularization. Moreover, while intermittent PTH is anti-osteoporotic, continuous PTH administration can be catabolic for bone. Finally...

La osteomalacia es una osteopatía metabólica que afecta a todo el esqueleto. Se caracteriza por el retraso de la mineralización de la matriz ósea recién formada y conduce a la acumulación de tejido osteoide. Acarrea una mayor fragilidad ósea, con la consiguiente aparición de fracturas o de fisuras espontáneas, sobre todo en las costillas, la pelvis...

Assessing bone turnover is a key diagnostic tool in the global management of chronic kidney disease-mineral and bone disorder (CKD-MBD). Since bone biopsy is invasive and cannot be repeated in clinical practice and because bone histomorphometry is less available due to the lack of specialized laboratories, we will focus on potential biomarkers used...

Vitamin D deficiency/insufficiency is significantly prevalent in chronic kidney disease. Data in the literature are however scarce about the effects of this deficiency on bone metabolism in hemodialysis (HD) patients. Moreover, it is still debated whether low vitamin D levels should be normalized in HD patients. In this paper, we report two cases s...

Bone and energetic metabolism are functionally linked. Type 2 diabetes increases bone fragility the pathophysiology of which is complex and includes a iatrogenic aspect. Among anti-diabetic drugs, thiazolidinediones, afgonists of PPAR-gamma, a transcritpion factor, increase fracture risk, especially in women after 65. The new treatments modulating...

The physiological role of bone vascularisation in bone metabolism begins to be understood, however its involvement in pathological situations remains poorly explored. Bone blood supply depends on both vascular density and blood flow. However, in mice, the specific evaluation of perfusion in bone suffers from a lack of easy-handling measurement tool...

The osteocyte cell network in bone tissue is thought to orchestrate tissue adaptation and remodeling, thus holding responsibility for tissue quality. Previously, this structure has been studied mainly in 2D and its architecture and functions are not fully elucidated. The assessment of the osteocyte system is prerequisite for deeper understanding of...

Treatment of vitamin D deficiency with vitamin D is a common procedure when taking care of elderly patients, calcium supplementation being added only when calcium dietary intake is insufficient. Here, we report the case of a 58-year-old female who was referred to our unit because of suspicion of Paget's disease of the skull, based on elevated serum...

1-Introduction: Bone vascularisation is the link between the many functions of the bone -organ Skeleton is an adaptable retro-controlled system which integrates mechanical, biochemical and nervous signals. Moreover, bone is a composite organ which fulfils several functions (locomotion, endocrine -with calcium/ phosphate and energetic metabolisms-,...

Chronic kidney disease (CKD) alters the metabolism of several minerals, thereby inducing bone lesions and vessel-wall calcifications that can cause functional impairments and excess mortality. The histological bone abnormalities seen in CKD, known as renal osteodystrophy, consist of alterations in the bone turnover rate, which may be increased (ost...

La maladie rénale chronique (MRC) induit des troubles du métabolisme des minéraux conduisant à des lésions osseuses et des calcifications vasculaires qui grèvent son pronostic vital et fonctionnel. L’atteinte osseuse est caractérisée par des lésions histologiques regroupées sous le nom d’ostéodystrophie rénale (ODR) : altération du niveau du turnov...

Background The target for serum parathyroid (PTH) hormone level in dialysis patients is higher than that in the normal population in order to prevent adynamic bone disease (ABD) that is associated with more frequent cardiovascular and bone disease. Based on biological and clinical data, we aimed at identifying the different types of low PTH (L-PTH)...

BACKGROUND: The target for serum parathyroid (PTH) hormone level in dialysis patients is higher than that in the normal population in order to prevent adynamic bone disease (ABD) that is associated with more frequent cardiovascular and bone disease. Based on biological and clinical data, we aimed at identifying the different types of low PTH (L-PTH...

We present a method for phase microtomography based on X-ray propagation based phase contrast imaging for multi-material objects. Previously, homogeneous composition assumptions have been in the Radon domain to overcome low sensitivity in the low frequency range. Here, we introduce a prior in the object domain based on multiple, but known, material...

Bone sialoprotein (BSP) is highly expressed in early bone deposition and may play a part in primary bone mineralization. We previously showed that while BSP−/− mice have a mild secondary bone phenotype and are responsive to mechanical (unloading) and hormonal (ovariectomy, parathyroid hormone (PTH)) challenges, repair of a cortical bone defect, whi...

Serum calcium levels are tightly controlled by an integrated hormone-controlled system that involves active vitamin D [1,25(OH)(2)D], which can elicit calcium mobilization from bone when intestinal calcium absorption is decreased. The skeletal adaptations, however, are still poorly characterized. To gain insight into these issues, we analyzed the c...

Bone marrow vascularisation is involved in both remodeling and hematopoiesis. Challenged mouse models often require imaging and quantitative assessment of blood vessels and bone cell activities for a better understanding of the role of the vascular system. In this study we compared images of mouse hind limb long bone vascularisation after infusion...

El tejido óseo es una variedad de tejido conjuntivo caracterizada por una sustancia intercelular mineralizada. Cumple diversas funciones primordiales: mantiene el equilibrio fosfocálcico por acción de las hormonas calciótropas: hormona paratiroidea, vitamina D y calcitonina; es el sitio principal de la hematopoyesis en el adulto, y sostiene el apar...