Biofabrication of functional bone tissue: defining tissue-engineered scaffolds from nature.

Damage to bone leads to pain and loss of movement in the musculoskeletal system. Although bone can regenerate, sometimes it is damaged beyond its innate capacity. Research interest is increasingly turning to tissue engineering (TE) processes to provide a clinical solution for bone defects. Despite the increasing biomimicry of tissue-engineered scaffolds, significant gaps remain in creating the complex bone substitutes, which include the biochemical and physical conditions required to recapitulate bone cells' natural growth, differentiation and maturation. Combining advanced biomaterials with new additive manufacturing technologies allows the development of 3D tissue, capable of forming cell aggregates and organoids based on natural and stimulated cues. Here, we provide an overview of the structure and mechanical properties of natural bone, the role of bone cells, the remodelling process, cytokines and signalling pathways, causes of bone defects and typical treatments and new TE strategies. We highlight processes of selecting biomaterials, cells and growth factors. Finally, we discuss innovative tissue-engineered models that have physiological and anatomical relevance for cancer treatments, injectable stimuli gels, and other therapeutic drug delivery systems. We also review current challenges and prospects of bone TE. Overall, this review serves as guide to understand and develop better tissue-engineered bone designs.

Antipsychotic medication use and fracture: a case-control study.

It has been reported that antipsychotic use is associated with lower bone mineral density and bone quality. We aimed to determine whether antipsychotic use is associated with fracture risk in a population-based sample of adults living in the Barwon Statistical Division, south-eastern Australia. In this case-control study, 1458 participants (51.8% women) with radiologically confirmed fracture between June 1st 2012 and May 31st 2013 (cases) were compared with 1795 participants (46.5% women) without fracture (controls) for the same time period. Medication use, medical history and lifestyle factors were documented by self-report. Multivariable binary logistic regression was used to explore associations between antipsychotic use and fracture following adjustment for possible confounders. In women, antipsychotic use was identified for 20 of 755 (2.6%) cases and 10 of 834 (1.2%) controls (p = 0.034) and in men, antipsychotic use was identified for 13 of 703 (1.8%) cases and 5 of 961 (0.5%) controls (p = 0.010). Following adjustments, antipsychotic use was associated with a 3.0-fold increased risk of fracture in men and a 2.3-fold increased risk of fracture in women. Patterns persisted after exclusion of participants with non-fragility fractures and self-reported schizophrenia. While future research exploring underlying mechanisms is needed, regular monitoring of bone health in antipsychotic users is suggested.

Antipsychotic medication use in association with quantitative heel ultrasound (QUS).

Purpose: Antipsychotic medication use has been associated with decreased bone mineral density; however, less is known whether antipsychotics affect other parameters of bone health. Therefore, the aim of this study was to investigate the association between antipsychotic medication use and quantitative heel ultrasound (QUS) in a population based sample of men and women. Methods: Thirty-one antipsychotic users and 155 non-users matched for age and sex were drawn from the Geelong Osteoporosis Study. QUS was undertaken and included the parameters: Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI). Current medication use, lifestyle factors, anthropometry and socio-economic status were collected. Generalized Estimation Equation models were conducted to determine associations between antipsychotic medication use and each of the QUS parameters, adjusting for covariates. Results: Antipsychotic users were less active, consumed less alcohol, were more likely to smoke and take antidepressants; otherwise, the groups were similar. After adjusting for age, sex and weight, antipsychotic users had a 7.7 % lower mean BUA [108.70 (95 % CI 104.26-113.14) vs. 116.42 (95 % CI 115.48-117.37) dB/MHz, p = 0.005] and 7.4 % lower mean SI [89.92 (95 % CI 86.89-92.95) vs. 97.30 (95 % CI 96.48-98.12) %, p < 0.001] compared to non-users. Differences in mean SOS between antipsychotic users and non-users failed to reach statistical significance (p = 0.07). Conclusion: Antipsychotic use was associated with lower QUS parameters. The risk of bone deterioration should be considered when antipsychotics are prescribed.

Antipsychotic-induced bone loss: the role of dopamine, serotonin and adrenergic receptor signalling.

Antipsychotics are commonly used in treating psychiatric disorders. These medications primarily target dopamine the serotonin receptors, they have some affinity to adrenergic, histamine, glutamate and muscarinic receptors. There is clinical evidence that antipsychotic use decreases BMD and increases fracture risk, with dopamine, serotonin and adrenergic receptor-signalling becoming an increasing area of focus where the presence of these receptors in osteoclasts and osteoblasts have been demonstrated. Osteoclasts and osteoblasts are the most important cells in the bone remodelling and the bone regeneration process where the activity of these cells determine the bone resorption and formation process in order to maintain healthy bone. However, an imbalance in osteoclast and osteoblast activity can lead to decreased BMD and increased fracture risk, which is also believed to be exacerbated by antipsychotics use. Therefore, the aim of this review is to provide an overview of the mechanisms of action of first, second and third generation antipsychotics and the expression profiles of dopamine, serotonin and adrenergic receptors during osteoclastogenesis and osteoblastogenesis.

Use of antipsychotic medication and its relationship with bone mineral density: A population-based study of men and women.

Background: Schizophrenia has been shown to be associated with reduced bone mineral density (BMD) and higher fracture risk. However, less is known whether antipsychotic treatment is associated with reduced BMD. Thus, we aimed to examine associations between antipsychotic use and BMD among men and women drawn from the general population. Methods: This cross-sectional study involved 793 women and 587 men enrolled in the Geelong Osteoporosis Study (GOS). BMD was determined using dual-energy X-ray absorptiometry at the spine and hip. Information regarding socio-economic status (SES), current medication and/or supplementation use, lifestyle factors, and anthropometry was collected. Association between antipsychotic use and BMD was determined using linear regression after adjusting for potential confounders. Results: Of the group, 33 women (4.2%) and 16 men (2.7%) currently used antipsychotics. Age was identified as an effect modifier in the association between antipsychotic use and BMD for women. Amongst women aged < 60 years, adjusted mean BMD was 11.1% lower at the spine [1.139 (95%CI 1.063-1.216) vs. 1.250 (95%CI 1.223-1.277) g/cm2, p = 0.005] for antipsychotic users compared to non-users. At the hip, age, weight, and smoking adjusted mean BMD was 9.9% lower [0.893 (95%CI 0.837-0.950) vs. 0.992 (95%CI 0.976-1.007) g/cm2, p < 0.001] for antipsychotic users in comparison with non-users. The pattern persisted following further adjustments. There was no association detected between antipsychotic use and BMD for women aged 60 years and over and for men. Conclusion: Our data suggest that antipsychotic medication use is associated with reduced BMD in younger women but not older women or men.