Osteoporos, även benämnt som benskörhet är en metabol skelettsjukdom vilken karakteriseras av nedgång i bentäthet samt en förändrad mikroarkitektur i skelettet vilket ger en ökad risk för frakturer. Hela 120 000 osteoporosrelaterade frakturer diagnostiserades 2017, vilka belastade den svenska sjukvården med 20 miljarder kronor. Den årliga förekomsten av osteoporosrelaterade frakturer förväntas öka med en ökad äldre population och en förändrad livsstil, vilket i sin tur kommer leda till ökade sjukvårdskostnader. Idag finns flera godkända läkemedel mot osteoporos och i första hand rekommenderas de antiresorptiva läkemedlet alendronat och därefter denosumab. Följsamheten till alendronat är dock väldigt låg och beror främst på de biverkningar som medföljer behandlingen. Patienter som inte svarar på behandling med antiresorptiva läkemedel kan övergå till anabola läkemedel, där teriparatid varit det enda tillgängliga läkemedlet. Under 2019 godkändes ytterligare ett anabolt läkemedel, romosozumab som en monoklonal antikropp riktad mot sklerostin. Romosozumabs anabola effekt utgörs genom att det selektivt binder till sklerostin vilket omöjliggör dess naturliga inhibering av den kanoniska Wingless-int -signaleringsvägen, vilket resulterar i en ökad benbildning genom en ökad osteoblastdifferentiering samt osteoprotegerin -medierad supersession av osteoklaster. Syftet med litteraturstudien var att undersöka läkemedelet romosozumab vid behandling av osteoporos hos postmenopausala kvinnor. Är romosozumab effektivt som initial behandling, som initialbehandling följt av antiresorptiv behandling och vid insättning efter terpi med antiresorptiva läkemedel? För att besvara denna frågeställningen undersöktes två olika variabler: Läkemedlets påverkan på bentäthet och frakturrisk och läkemedlets effektivitet jämfört med andra behandlingsalternativ. Litteraturstudien baserades på en analys av fem kliniska studier där data gällande förändring av bentäthet (BMD) och incidens av ny fraktur presenterades. Resultatet visade att initial behandling med romozozumab under 12 månader gav en statistiskt signifikant ökning av BMD om 11.3-13.7% samtidigt som frakturrisken visades var lägre jämfört med placebo, teriparatid, denosumab och alendronat. Ökningen av BMD och den minskade frakturrisken bibehölls efter 12 månaders underhållsbehandling med antiresorptiva läkemedel. Däremot kunde inga slutsatser dras kring hur länge romosozumabs effekt kan bibehållas vid underhållsbehandling med antiresorptiva och inte heller vilken effekt romosozumab har hos patienter som sedan tidigare administrerats antiresorptiva läkemedel. / Osteoporosis, also referred as bone fragility is a metabolic bone disease characterized by a decrease in bone density as well as a altered bone microarchitecture, which increase the risk of fractures. As many as 120,000 osteoporosis-related fractures were diagnosed in 2017, and an economic burden on the Swedish healthcare system was 20 billion SEK. With an aging population and a change lifestyle, the annual incidence of osteoporosis- related fractures are expected to increase, which in turn will lead to increased healthcare costs. During the first years of life bone modeling occurs, a process of bone formation. After completed modeling the bone will continually undergo a resorption and modeling, a process referred to as remodeling. The remodeling is estimated to occour at 1-2 million different locations in the bone simultaneously. The cells involved in this process are osteoclasts that resorbs bones, osteoblasts that build up bones and osteocytes that can stimulate the bone-forming ability of osteoblasts and osteoclasts for resorption when rebuilding old bone. During the continuous process of remodeling the bone resorption and formation are equal, in diseases such as osteoporosis the bone resorption is greater than bone formation. Today there are several approved drugs for osteoporosis and the most widely used are the antiresorptive drugs bisphosphonates followed by denosumab. Though the adherence to bisphosphonates are very low and mainly due to the side effects that come with the treatment. Patients who do not respond to antiresorptive therapy may switch to anabolic drugs, where teriparatide was previously the only drug available. In 2019, another anabolic drug, named romosozumab was approved, a humanized monoclonal antibody specifically targeted against the protein sclerostin. Romosozumab blocks sclerostin from binding to low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6) on osteoblasts which allows activation of the intracellular wingless-int signaling pathway that actives transkiption of target genes. The primarily target genes for the activation of LRP5/6 are genes involved in osteoblast differentiation but also genes for osteoprotegerin which inhibit osteoclasts differentiation through binding to receptor activator of nuclear factor kappa-Β ligand (RANKL). The purpose of this literature study was to investigate the drug romosozumab as treatment of osteoporosis in postmenopausal women: Is romosozumab effective as initial treatment, as initialtreatment followed by resorptive therapy and upon post-therapy with antiresorptive drugs? Romosozumab is a relatively new drug on the market, therefore there is a limited number of published clinical trials and conclusions drawn regarding if the long-term effect of romosozumab can be maintained in antiresorptive maintenance therapy, nor about the effect of the drug in patients previously administrated antiresorptive therapy. To answer the purpose of the literature study, two different variables were examined: the drugs impact on bone mineral density (BMD) and fracture risk, and the drug’s effectiveness compared to other treatment options. Five clinical trials were selected for analysis based on the purpose of the literature study from the two medical reference databases: PubMed and ClinicalTrials.gov. The data from the analyzed studies showed that by using romosozumab as initial treatment for 12 months resulted in a statistically significant increase in BMD of 11.3–13.7% at the same time as the risk of a new fracture was lowered compared to placebo, teriparatide, denosumab and alendronat. The increase in BMD and the reduced fracture risk were maintained during the 12-month follow-up treatment with antiresorptive drugs.

Astronauts at are risk of losing 1.0-1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and diets high in nutrients, potassium, calcium, and vitamin D, all designed to preserve the skeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth factor-1 and its receptor insulin-like growth factor-1 receptor (GFR1) play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.