Orchestration of bone remodeling

In healthy individuals, a balance exists between bone formation and resorption. Disruption of this balance can lead to higher or lower bone mass, and disease such as osteoporosis. Treatment for osteoporosis generally inhibits bone resorption, but does not rebuild bone to a healthy strength. More knowledge on bone metabolism and new therapeutic strategies is therefore needed. Sclerostin is a protein that inhibits bone formation and is produced by osteocytes in mineralized bone matrix. Due to this specific localization and function it is viewed as one of the most interesting targets for new osteoporosis therapies. The first part of this thesis is focused on the effect of sclerostin in patients. People with inactivating mutations in sclerostin have a strongly increased bone mass. They show the effect of decreased production, and investigating these patients therefore increases knowledge on sclerostin__s mechanism of action. The regulation of sclerostin has been investigated in the second part of this thesis. In addition, antisense oligonucleotides have been used in exon skipping to decrease sclerostin expression. Finally, a new method for quantification of in vitro mineralization of bone cells was developed. This method is easy and scalable and can therefore contribute to future research into new osteoporosis therapies.Nederlandse vereniging voor Calcium- en Botstofwisseling, Greiner Bio-OneUBL - phd migration 201

Positive health during the COVID-19 pandemic: a survey among community-dwelling older individuals in the Netherlands

Abstract Background Coronavirus Disease 2019 (COVID-19) reached the Netherlands in February 2020. To minimize the spread of the virus, the Dutch government announced an “intelligent lockdown”. Older individuals were urged to socially isolate completely, because they are at risk of a severe disease course. Although isolation reduces the medical impact of the virus, the non-medical impact should also be considered. Aim To investigate the impact of COVID-19 pandemic and associated restrictive measures on the six dimensions of Positive Health in community-dwelling older individuals living in the Netherlands, and to identify differences within subgroups. Methods In May/June 2020, community-dwelling older individuals aged ≥ 65 years completed an online survey based on Huber’s model of Positive Health. Positive Health was measured regarding the appreciation of the six dimensions (categorized as poor/satisfactory/excellent) and a comparison with a year before (categorized as decreased/unchanged/increased) using frequencies (%) and a chi-square test. Results 834 older individuals participated (51% women, 38% aged ≥ 76 years, 35% living alone, 16% self-rated poor health). Most respondents assessed their bodily functions, mental well-being and daily functioning as satisfactory, their meaningfulness and quality of life (QoL) as excellent, and their social participation as poor. 12% of the respondents reported a deterioration of 4–6 dimensions and 73% in 1–3 dimensions, compared to the past year. Deterioration was most frequently experienced in the dimension social participation (73%), the dimension mental well-being was most frequently improved (37%) and quality of life was in 71% rated as unchanged. Women more often observed a deterioration of 4–6 dimensions than men (15% vs. 8%, p = 0.001), and individuals with self-rated poor health more often than individuals with self-rated good health (22% vs. 10%, p < 0.001). Older individuals living alone experienced more frequently a decrease in meaningfulness compared to older individuals living together. Conclusion The COVID-19 pandemic and associated restrictive measures had a substantial impact on all six dimensions of Positive Health in community-dwelling older individuals, especially in women, respondents living alone and respondents with self-rated poor general health.Development and application of statistical models for medical scientific researc

Serum Dickkopf 1 Levels in Sclerostin Deficiency

Bone and mineral researc

Validation of an easy new method to quantify in vitro mineralization using Bonetag or Osteosense

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Inhibition of GSK3 Stimulates BMP Signaling and Decreases SOST Expression Which Results in Enhanced Osteoblast Differentiation

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Validation of a simple and fast method to quantify in vitro mineralization with fluorescent probes used in molecular imaging of bone

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas