Relationship Between Osteonecrosis of the Jaw and Bisphosphonate Treatment

Terapija bisfosfonatima i njezina etiopatogenetska povezanost s aseptičkom osteonekrozom čeljusti važan je javnozdravstveni problem današnjice. Svrha je rada pregledom suvremene znanstvene literature utvrditi posljedice višestrukog djelovanja bisfosfonata (antiosteoklastična aktivnost, citotoksičnost na meka i koštana tkiva, antiangiogeneza, genski čimbenici, poremećena ravnoteža između osteoklasta i osteoblasta). Terapija bisfosfonatima jedan je od najčešćih uzroka razvoja osteonekroze čeljusti. Epidemiološki podaci pokazuju da se javlja u bolesnika koji su uzimali jedan ili kombinanciju nitrogenih bisfosfonata. Najvažniji čimbenici rizika za ovu nuspojavu su vrsta bisfosfonata (napose visokopotentni pamidronat i zoledronat koji se daju intravenski), njihova doza i duljina medikacije te vrsta bolesti zbog koje se propisuje terapija. Pojava osteonekroze čeljusti zabilježena je uglavnom u onkoloških bolesnika i u samo 5 % bolesnika s osteoporozom koji su liječeni bisfosfonatima. U patogenezi osteonekroze povezane s bisfosfonatima važno je, sa stajališta dentalnomedicinske prakse, dobro opće oralno zdravlje jer se osteonekroza javlja napose nakon prethodnoga parodontološkog i oralnokirurškog zahvata.Bisphosphonate treatment and its aetiopathogenic association with aseptic osteonecrosis of the jaw is one of the more prominent public health issues today. The aim of this review is to see into the mechanisms of bisphosphonate effects on bones described in literature (anti-osteoclastic activity, cytotoxicity, antiangiogenesis, genetic factors, and imbalance between osteoclasts and osteoblasts). Bisphosphonate treatment is the dominant cause of jaw necrosis. Epidemiological data show an exclusive incidence of osteonecrosis of the jaw in patients who took one or a combination of nitrogen-containing bisphosphonates. Risk factors vary by the bisphosphonate potency (particularly risky are the highly potent pamidronate and zoledronate, which are given intravenously), dosage, duration of treatment, and the illness. Jaw necrosis is most common in oncology patients, and only 5 % in patients with osteoporosis. From a dental-medical point of view, a good oral health is important because osteonecrosis often appears after a periodontal or oral surgical procedure

Role of the cholesterol biosynthetic pathway in osteoblastic differentiation

Cholesterol (C27H46O) is the principal structural lipid of the biological membrane, but it also plays an important role in many other biological functions. Even though the majority of body cholesterol is synthesized by the liver and secreted as circulating lipoproteins, many cell types can synthesize cholesterol ex novo. The biosynthetic pathway of cholesterol proceeds through several intermediates and involves different enzymes. The rate-limiting step of cholesterol synthesis is the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that synthesizes mevalonate starting from HMG-CoA. Since natural inhibitors of HMG-CoA reductase, named statin, have been isolated, many others have been developed, which differ in their lipophilicity/ hydrophilicity. By using statins, many studies have been performed in order to shed light on the role of cholesterol on different cell types and, among these, on bone cells. In vivo studies have demonstrated that treatment of pluripotent mouse marrow stromal cells (M2-10B4) with statins inhibited the differentiation of these cells into osteoblastic cells, confirming the crucial role of cholesterol biosynthetic pathway for osteoblast differentiation. Conversely, other studies, using other cellular systems, have reported that statins may exert an anabolic effect on bone. Moreover, human and animal studies have shown that hypercholesterolemia may play an adverse effect in osteoporotic bone loss. In conclusion, it appears that cholesterol is important for different cellular activities, such as osteoblastic differentiation, if present in "normal" physiological concentration and particular experimental conditions, but it may exert adverse effects if present in excess

The role of PPAR? for the osteoblastic differentiation.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily and functions as a heterodimer with a retinoid X receptor by binding to PPAR responsive elements. PPARγ plays an important role in adipocyte differentiation and is activated by long-chain fatty acid, peroxisome proliferators, and thiazolidinedione (TZD). TZD are agonists of PPARγ, act as insulin-sensitizing agents, and are widely prescribed in the management of different conditions characterized by insulin resistance. Osteoblasts and marrow adipocytes derive from common multipotential mesenchymal stem cell (MSC) progenitors. Lineage commitment of MSC is determined by expression and/or activation of specific transcription factors, such as Runx2 and Osterix in the case of osteoblasts, and PPARγ in the case of adipocytes. Many evidences indicate an important role of PPARγ in bone metabolism. Heterozygous PPARγ-deficient (PPARγ +/-) mice exhibit enhanced bone formation with increased osteoblastogenesis. Embryonic stem cells derived from PPARγ +/- mice spontaneously differentiate into osteoblasts. In mice and rats, the activation of PPARγ by TZD treatment, such as rosiglitazone (Rosi), causes bone loss, which results from an increase of marrow adipocytes and a decrease of osteoblasts, leading to a reduction of bone formation rate. Human studies have shown that pre- and post-menopausal women treated with Rosi have an increased risk of fracture compared to women treated with metformin and glyburide. Moreover, the modulation of the PPARγ expression is also implicated in the effects of mechanical loading on bone and in age-related bone loss

Characterisation of an Additively Manufactured 3D Cross-Based Fractal Structure for Impact Energy Absorption

Designers propose using high-performance materials or cellular and bio-inspired structures in components with high strength-to-weight ratios, high heat transfer capacity, and energy absorption. An example is fractal geometries, which show highly complex 3D geometries that are unfeasible using conventional manufacturing processes. The work investigates the energy absorption performances of a 3D cross-based fractal structure (3D-CFS). The geometry is inspired by the mathematical 3D Greek cross geometry and designed for production using Additive Manufacturing (AM) powder bed fusion processes for polymers (PBF). The mechanical properties of Polyamide (PA12) and Thermoplastic Polyurethane (TPU) 3D-CFS structures designed with different volume fractions are evaluated using quasi-static and dynamic compression tests. The results show that the 3D-CFS structure is a good candidate for shock absorption applications such as personal protective equipment (PPE) applications