Liesbeth Winter

Leiden University Medical Centre | LUMC · Department of Endocrinology and General Internal Medicine

Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic bone disease caused by a somatic mutation in the GNAS gene. Currently used bone turnover markers (BTMs) do not correlate with the clinical picture and are not useful to predict or monitor therapy success. This study assessed the correlation of RANKL, OPG, RANKL/OPG r...

Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a tertiary multidisciplinary care pathway, but no longitudinal data are available to support this recommendation. This multicenter prospective observation...

Objectives Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular hyperostosis (SCCH) and mainly occurs in adults. Literature on CNO/SCCH is scattered, and lacks diagnostic and therapeutic consensus. Methods Systematic...

Editorial: Glucocorticoid and bone: friend or foe Introduction Glucocorticoids have potent anti‑inflammatory effects and their discovery in 1948 improved therapy for many diseases with chronic inflammation noticeably. However, glucocorticoid treatment causes severe side effects, including bone loss and increased fracture risk. The first studies on...

Background Sternocostoclavicular hyperostosis (SCCH) is an inflammatory bone disorder within the spectrum of chronic non-bacterial osteomyelitis. SCCH can be a manifestation of SAPHO syndrome, standing acronym for synovitis, acne, pustulosis, hyperostosis and osteitis, but also appears as an isolated clinical entity without joint and skin involveme...

Sternocostoclavicular hyperostosis (SCCH), the main clinical manifestation of chronic non-bacterial osteomyelitis (CNO) in adults, is associated with various degrees of chronic pain and restricted shoulder girdle function. We evaluated the impact of CNO/SCCH on quality of life (QoL) and its determinants in 136 adult patients with this rare auto-inf...

Bone material properties were assessed using impact microindentation in patients with high-energy trauma fractures. Compared to patients with low-energy trauma fractures, bone material strength index was significantly higher in patients with high-energy trauma fractures, and did not differ between patients with osteopenia and those with osteoporosi...

[This corrects the article DOI: 10.3389/fendo.2021.782118.].

Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a tertiary multidisciplinary care pathway, but no longitudinal data are available to support this recommendation. This multicenter prospective observationa...

Over the last two decades there have been significant developments in the pharmacotherapy of osteoporosis. The therapeutic arsenal has expanded with monoclonal antibodies which have been developed based on discoveries of the molecular mechanisms underlying bone resorption and bone formation. Denosumab, the antibody binding RANKL, inhibits bone reso...

Glucocorticoid-induced osteoporosis (GIOP) leads to fractures in up to 40% of patients with chronic glucocorticoid (GC) therapy when left untreated. GCs rapidly increase fracture risk, and thus many patients with anticipated chronic GC exposures should start anti-osteoporosis pharmacotherapy to prevent fractures. In addition to low awareness of the...

This is a survey study concerning osteoporosis care during the COVID-19 pandemic in the Netherlands. Respondents reported that osteoporosis care stagnated and lower quality of care was provided. This leads to the conclusion that standardization of osteoporosis care delivery in situations of crisis is needed. Purpose: During the initial phase of t...

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Pro...

Purpose of Review Fractures are frequently encountered in paediatric practice. Although recurrent fractures in children usually unveil a monogenic syndrome, paediatric fracture risk could be shaped by the individual genetic background influencing the acquisition of bone mineral density, and therefore, the skeletal fragility as shown in adults. Here...

Glucocorticoid (GC)-induced osteoporosis is a widespread health problem that is accompanied with increased fracture risk. Detrimental effects of anti-inflammatory GC therapy on bone have been ascribed to the excess in GC exposure, but it is unknown whether there is also a role for disruption of the endogenous GC rhythm that is inherent to GC therap...

Denosumab treatment can benefit patients with fibrous dysplasia/McCune‐Albright Syndrome (FD/MAS) by suppressing the RANKL‐mediated increased bone resorption. However, limited data of two pediatric cases indicate that a rebound phenomenon may occur after withdrawal. Therefore we studied the safety of denosumab discontinuation in FD/MAS. Thirty‐seve...

Context Zoledronate is used to prevent bone loss following denosumab discontinuation but its efficacy differs among studies. Objective To test if the duration of denosumab treatment affects the efficacy of subsequent zoledronate infusion. Design Multicenter, prospective cohort study. Setting Two Greek and one Dutch bone centers. Patients Postme...

Physiological circadian (i.e., 24‐hour) rhythms are critical for bone health. Animal studies have shown that genes involved in the intrinsic molecular clock demonstrate potent circadian expression patterns in bone, and that genetic disruption of these clock genes results in a disturbed bone structure and quality. More importantly, circulating marke...

Background: Cardiovascular safety concerns for major cardiovascular events (MACE) were raised during the clinical trials of romosozumab. We aimed to evaluate the cardiovascular safety profile of romosozumab in a large pharmacovigilance database. Methods: All cases reported between January 2019 and December 2020 where romosozumab was reported were e...

Context The correlation between Fibrous Dysplasia/McCune-Albright syndrome (FD/MAS) skeletal disease burden on Na[18F]F-PET-CT and serum bone turnover markers (BTMs) was recently described. The effect of treatment on lesional fluoride burden in FD/MAS is unknown. Objective To investigate treatment response measurements in FD/MAS patients who under...

Context In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bo...

Sternocostoclavicular hyperostosis (SCCH) is a rare auto‐inflammatory bone disorder due to a chronic non‐bacterial osteomyelitis (CNO), associated with sclerosis and hyperostosis primarily affecting sternum, medial end of clavicles and first ribs (SCCH). Other areas of the axial skeleton may be affected. The more severe synovitis‐acne‐pustulosis‐hy...

Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for...

Diagnosing and treating hypercalcemia during pregnancy can be challenging due to both the physiological changes in calcium homeostasis and the underlying cause for the hypercalcemia. During pregnancy and lactation there is increased mobilization of calcium in the mother to meet the fetus’ calcium requirements. Here we discuss the diagnostic challen...

Osteoporosis is a long-term consequence of spinal cord injury (SCI) that leads to a high risk of fragility fractures. The fracture rate in people with SCI is twice that of the general population. At least 50% of these fractures are associated with clinical complications such as infections. This review article presents key features of osteoporosis a...

Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risk of fragility fractures and significant long-term disability. Although both anti-resorptive treatments and osteoanabolic drugs, such as parathyroid hormone analogues, are effective in fracture prevention, limitations exist due to lack...

Background Sternocostoclavicular hyperostosis (SCCH) is a rare disease, constituting a chronic sterile osteomyelitis with elevated bone turnover in the axial skeleton, causing pain and shoulder dysfunction. SCCH severely interferes with daily activities, work, and quality of life. SCCH has a relapse-remitting disease course, but inflammatory-induce...

In this review we discuss skeletal adaptations to the demanding situation of pregnancy and lactation. Calcium demands are increased during pregnancy and lactation, and this is effectuated by a complex series of hormonal changes. The changes in bone structure at the tissue and whole bone level observed during pregnancy and lactation appear to largel...

Effects on bone material properties of two-year antiosteoporotic treatment were assessed using in vivo impact microindentation (IMI) in patients with low bone mineral density (BMD) values. Antiresorptive treatment, in contrast to vitamin D ± calcium treatment alone, induced BMD-independent increases in bone material strength index, measured by IMI,...

The current gold standard for the diagnosis of osteoporosis and the prediction of fracture risk is the measurement of bone mineral density (BMD) using dual energy x-ray absorptiometry (DXA). A low BMD is clearly associated with increased fracture risk, but BMD is not the only determinant of bone strength, particularly in secondary osteoporosis and...

The past decade, it has become evident that circadian rhythms within metabolically active tissues are very important for physical health. However, although shift work has also been associated with an increased risk of fractures, circadian rhythmicity has not yet been extensively studied in bone. Here, we investigated which genes are rhythmically ex...

Background: Systemic exposure to high-dose corticosteroids effectively combats acute rejection after kidney transplantation, but at the cost of substantial side effects. In this study, a murine acute renal allograft rejection model was used to investigate whether liposomal encapsulated prednisolone (LP) facilitates local exposure to enhance its th...

Context Parathyroid hormone related protein (PTH-rP) induced hypercalcemia or pseudophyperparathyroidism during pregnancy is a condition that can result in serious foetal and maternal complications. Among others, breast tissue might be the cause of this PTH-rP production, in which case medical treatment is possible, as we describe in this case. Se...

Paget's disease of bone is a focal disorder of bone remodelling that leads to changes in the shape and size of affected bones, and is associated with articular and vascular complications. The disorder is characterised by a localised increase in osteoclast number and activity in one or more affected sites while the rest of the skeleton remains unaff...

The significance of the epicardium that covers the heart and the roots of the great arteries should not be underestimated as it is a major component with impact on development, disease, and repair. The epicardium differentiates from the proepicardial organ located at the venous pole (vPEO). The differentiation capacities of the vPEO into epicardium...

This is the first report of unilateral hypercortisolism and phaeochromocytoma that cannot be explained by medullary tumourigenic adrenocorticotropic hormone (ACTH) excretion. The patient was referred for an adrenal incidentaloma with hypertension but no Cushingoid features, disturbed glucose tolerance and osteopaenia. Additional testing revealed hy...

The importance of the epicardium covering the heart and the intrapericardial part of the great arteries has reached a new summit. It has evolved as a major cellular component with impact both in development, disease and more recently also repair potential. The role of the epicardium in development, its differentiation from a proepicardial organ at...

The myocardium of the developing heart tube is covered by epicardium. These epicardial cells undergo a process of epithelial-to-mesenchymal transformation (EMT) and develop into epicardium-derived cells (EPDCs). The ingrowing EPDCs differentiate into several celltypes of which the cardiac fibroblasts form the main group. Disturbance of EMT of the e...

We previously showed that human cardiomyocyte progenitor cells (hCMPCs) injected after myocardial infarction (MI) had differentiated into cardiomyocytes in vivo 3 months after MI. Here, we investigated the short-term (2 weeks) effects of hCMPCs on the infarcted mouse myocardium. MI was induced in immunocompromised (NOD/scid) mice, immediately follo...

During heart development, cells from the proepicardial organ spread over the naked heart tube to form the epicardium. From here, epicardium-derived cells (EPDCs) migrate into the myocardium. EPDCs proved to be indispensable for the formation of the ventricular compact zone and myocardial maturation, by largely unknown mechanisms. In this study we i...

Reactivation of endogenous epicardium after ischemia The proepicardial-derived epicardium covers the myocardium and after a process of epithelial-mesenchymal transition (EMT) forms epicardium-derived cells (EPDCs). These cells migrate into the myocardium and show an essential role in the induction of the ventricular compact myocardium and the diffe...

Adult human epicardium-derived cells (EPDCs), transplanted into the infarcted heart, are known to improve cardiac function, mainly through paracrine protection of the surrounding tissue. We hypothesized that this effect might be further improved if these supportive EPDCs were combined with cells that could possibly supply the ischemic heart with ne...

Murine myocardial infarction (MI) models are increasingly used in heart failure studies. Magnetic resonance imaging (MRI) and pressure-volume loops by conductance catheter (CC) enable physiological phenotyping. We performed a comparative analysis of MRI vs. CC to assess left ventricular (LV) function in the failing mouse heart. MI was created by LA...

Human mesenchymal stem cells (hMSCs) have only a limited differentiation potential toward cardiomyocytes. Forced expression of the cardiomyogenic transcription factor myocardin may stimulate hMSCs to acquire a cardiomyogenic phenotype, thereby improving their possible therapeutic potential. hMSCs were transduced with green fluorescent protein (GFP)...

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI mode...

Proper development of compact myocardium, coronary vessels, and Purkinje fibers depends on the presence of epicardium-derived cells (EPDCs) in embryonic myocardium. We hypothesized that adult human EPDCs might partly reactivate their embryonic program when transplanted into ischemic myocardium and improve cardiac performance after myocardial infarc...

During cardiogenesis, the epicardium grows from the proepicardial organ to form the outermost layer of the early heart. Part of the epicardium undergoes epithelial-mesenchymal transformation, and migrates into the myocardium. These epicardium-derived cells differentiate into interstitial fibroblasts, coronary smooth muscle cells, and perivascular f...

During cardiogenesis, the epicardium grows from the proepicardial organ to form the outermost layer of the early heart. Part of the epicardium undergoes epithelial-mesenchymal transformation, and migrates into the myocardium. These epicardium- derived cells differentiate into interstitial fibroblasts, coronary smooth muscle cells, and perivascular...

Myocardial and coronary development are both critically dependent on epicardial cells. During cardiomorphogenesis, a subset of epicardial cells undergoes an epithelial-to-mesenchymal transition (EMT) and invades the myocardium to differentiate into various cell types, including coronary smooth muscle cells and perivascular and cardiac interstitial...

During heart development, cells of the primary and secondary heart field give rise to the myocardial component of the heart. The neural crest and epicardium provide the heart with a considerable amount of nonmyocardial cells that are indispensable for correct heart development. During the past 2 decades, the importance of epicardium-derived cells (...