Tricyclic antidepressants are effective for managing depression and other disorders. However, they can cause adverse reactions due to their anticholinergic properties, with the risk of such events increasing with age. This study identifies and describes clinical studies that evaluate associations between the use of tricyclic antidepressants and adverse health outcomes (falls, fractures, and mortality) among older people. A systematic search of the literature in English, Spanish, and French was conducted using the electronic databases PubMed, ISI Web of Science, PsycINFO, and Cochrane. The systematic review included a total of 18 studies. The meta-analysis examined the 14 studies that investigated the association between the use of tricyclic antidepressants and the risk of falls and fractures (4 of the 18 studies focused on mortality and so were excluded from the meta-analysis). The odds ratio (OR) was 1.40 (95 % CI = 1.27-1.53, p < 0.001). The Cochran Q test was significant (X2 = 79.72, p < 0.001), indicating high heterogeneity (I2 = 84.9 %). An additional meta-analysis was conducted on studies reporting hazard ratios (HRs), yielding an HR of 1.21 (95 % CI = 0.93-1.58, p = 0.16). Meta-regression analysis indicated that the years of follow-up could have a significant effect on the association studied (p = 0.008). In conclusion, enhancing our understanding of the use of antidepressants and the associated risk of adverse events in older adults will enable the identification of the most appropriate type of antidepressant for each clinical situation.

Dental implant fractures pose a significant challenge to long-term treatment success. This systematic review aims to comprehensively examine the clinical factors influencing dental implant fractures (IFs). Furthermore, strategies to choose the right type of implant and prevent this complication are addressed. A systematic search was conducted across PubMed, Scopus, and Web of Science databases. Eligible studies included retrospective case-control, prospective cohort studies, and clinical trials. The initial search yielded 361 articles, of which 312 were excluded being these reviews, case reports, irrelevant, or written in languages other than English. This left 49 articles, with only 6 meeting the eligibility criteria for an in-depth review. These studies, all retrospective case-control, examine implant characteristics, patient demographics, surgical and prosthetic variables, biomechanical and functional factors, clinical and procedural variables, complications and maintenance issues. The risk of bias was assessed as low using the ROBINS-I tool. Key findings suggest a correlation between implant diameter and structural resistance, with wider implants demonstrating reduced fracture risk. Additionally, posterior regions, especially molars and premolars, exhibit higher susceptibility to IFs due to increased masticatory forces. Implant design and material may considerably influence fracture risk, with conical implants and screw-retained prostheses showing higher vulnerability. Biomechanical overload, particularly in patients with bruxism, emerges as a primary contributing factor to IFs. Prosthesis type significantly influences fracture incidence, with cantilever prostheses posing a higher risk due to increased stress. Peri-implant bone loss is strongly associated with IFs, emphasizing the need for meticulous preoperative assessments and individualized management strategies. Future research should prioritize larger and heterogeneous populations with long-term follow-up and standardized methodologies to enhance the generalizability and comparability of findings. Randomized controlled trials and biomechanical studies under controlled conditions are also essential to elucidate the complex interactions contributing to IFs and developing effective prevention strategies. Additionally, integrating patient-reported outcomes may offer a comprehensive understanding of the impact of IFs on quality of life.

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures.
METHODS: The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals.
CONCLUSIONS: The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body\'s mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4\'s effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.

As we age, maintaining good oral health becomes increasingly crucial for performing daily tasks. Age-related physiological decline can disrupt various biological systems, causing a significant challenge for geriatric dentistry. A systematic review of the literature using six different electronic databases was conducted to investigate the relationship between oral health indicators and bone mineral density disorders in older adults. The study is registered as a priori protocol on PROSPERO (CRD42023403340). A minimum age of 60 years was the main inclusion criterion for all original research articles. Two independent researchers assessed the eligibility of 19,362 records against the inclusion criteria and found 12 articles fitting the eligibility requirements. Five different indicators of poor oral health [number of teeth, periodontal disease, general oral health (dental caries prevalence and dental treatment needs), masticatory function, and occlusal force)] were found related to three outcomes linked to bone mineral density disorders (osteoporosis, fractures, and decreased bone mineral density), regardless of the adopted assessment tools. The number of teeth was negatively associated with fractures and a decreased bone mineral density, while periodontal disease was positively associated with osteoporosis and a decreased bone mineral density. Masticatory function was associated only with osteoporosis, while general oral health was associated only with fractures and occlusal force only with bone mineral density. The oral health indicator most frequently associated with outcomes linked to bone mineral density disorders was the number of teeth. The present findings could help to assess the contribution of each oral health indicator to the development of bone mineral density disorders in older age.

BACKGROUND: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap.
METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP).
RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery.
CONCLUSIONS: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

Adrenal adenomas/incidentalomas with mild autonomous cortisol secretion (MACS)/subclinical hypercortisolism (SH) are often associated with metabolic syndrome, glucocorticoid-induced osteoporosis, and fractures. In this background, the present systematic review and meta-analysis aimed to collate the available evidence and provide a summary of the effect of MACS/SH on bone health in terms of fractures, osteoporosis/osteopenia, microarchitecture, and bone turnover. PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched for observational studies reporting prevalence of fractures, osteoporosis/osteopenia or data on bone microarchitecture/bone turnover markers (BTMs). Following literature search, 16 observational studies were included. Pooled prevalence of any fractures (vertebral and non-vertebral), vertebral fractures, and osteoporosis/osteopenia in MACS/SH were 43% [95% confidence intervals (CI): 23%, 62%], 45% (95% CI: 22%, 68%) and 50% (95% CI: 33%, 66%), respectively. On meta-regression, age, sex, 24-hour urinary free cortisol, and dehydroepiandrosterone-sulfate did not predict fracture risk. The likelihood of any fractures [odds ratio (OR) 1.61; 95% CI: 1.18, 2.20; P = 0.0026], vertebral fractures (OR 2.10; 95% CI: 1.28, 3.45; P = 0.0035), and osteoporosis/osteopenia (OR 1.46; 95% CI: 1.15, 1.85; P = 0.0018) was significantly higher in adrenal adenomas and MACS/SH than non-functional adrenal adenomas. Subjects with MACS/SH had significantly lower bone mineral density (BMD) at lumbar spine [mean difference (MD) -0.07 g/cm2; 95% CI: -0.11, -0.03; P = 0.0004) and femoral neck (MD -0.05 g/cm2; 95% CI: -0.08, -0.02; P = 0.0045) than their non-functional counterparts. Limited data showed no significant difference in BTMs. Publication bias was observed in the pooled prevalence of any fractures, vertebral fractures and pooled MD of femoral neck BMD. To conclude, people with adrenal adenomas/incidentalomas and MACS/SH are at a 1.5- to 2-fold higher likelihood of fractures and osteoporosis/osteopenia compared to non-functional adrenal adenomas and should routinely be screened for bone disease. Nevertheless, considering the modest sample size of studies and evidence of publication bias, larger and high-quality studies are required (CRD42023471045).
Mild autonomous cortisol secretion (MACS), often also referred to as subclinical hypercortisolism (SH), is usually associated with an underlying adrenal incidentaloma (AI), an adrenal mass incidentally found during abdomen imaging. Although signs of overt cortisol excess are lacking, subjects with MACS/SH often have features of metabolic syndrome, osteoporosis and fractures. The present systematic review and meta-analysis showed that the pooled prevalence of any fractures (vertebral and non–vertebral), vertebral fractures, and osteoporosis/osteopenia in MACS/SH were 43%, 45%, and 50%, respectively. People with adrenal adenomas/incidentalomas and MACS/SH are at a 1.5- to 2-fold higher likelihood of fractures and osteoporosis/osteopenia compared to non–functional adrenal adenomas. Besides, subjects with MACS/SH had significantly lower bone mineral density at lumbar spine and femoral neck than their non–functional counterparts. It is thus imperative to assess bone health in all subjects with MACS/SH.

This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

UNASSIGNED: Fracture healing poses a significant challenge in orthopedics. Successful regeneration of bone is provided by mechanical stability and a favorable biological microenvironment. This systematic review aims to explore the clinical application of orthobiologics in treating aseptic delayed union and non-union of long bones in adults.
UNASSIGNED: A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Three databases were explored, with no date restrictions, using keywords related to orthobiologics and delayed union and non-union. Eligible studies included human clinical studies in English, with available full texts, examining orthobiologics such as platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), and bone morphogenetic protein (BMPs) for treating aseptic delayed unions and non-unions in adults. Animal studies, in vitro research, and studies on non-unions due to congenital defects, tumors or infections were excluded.
UNASSIGNED: The initial search identified 9417 studies, with 20 ultimately included in the review. These studies involved 493 patients affected by non-union and 256 patients affected by delayed union, with an average age respectively of 40.62 years and 41.7 years. The mean follow-up period was 15.55 months for non-unions and 8.07 months for delayed unions. PRP was the most used orthobiologic, and outcomes were evaluated through time to union, functional scores, and clinical examinations. The results indicated that orthobiologics, especially PRP, tended to yield better outcomes compared to surgical procedures without biological factors.
UNASSIGNED: This systematic review suggests that orthobiologics, such as PRP, BMPs, and MSCs, can be effective and safe in the management of delayed union and non-union fractures. These biological treatments have the potential to improve union rates, reduce healing times, and enhance functional outcomes in patients with non-union fractures. Further research is essential to refine treatment protocols and determine the most suitable orthobiologic for specific patient populations and fracture types.

Osteopetrosis refers to a group of related rare bone diseases characterized by a high bone mass due to impaired bone resorption by osteoclasts. Despite the high bone mass, skeletal strength is compromised and the risk of fracture is high, particularly in the long bones. Osteopetrosis was classically categorized by inheritance pattern into autosomal recessive forms (ARO), which are severe and diagnosed within the first years of life, an intermediate form and an autosomal dominant (ADO) form; the latter with variable clinical severity and typically diagnosed during adolescence or in young adulthood. Subsequently, the AD form was shown to be a result of mutations in the gene CLCN7 encoding for the ClC-7 chloride channel). Traditionally, the diagnosis of osteopetrosis was made on radiograph appearance alone, but recent molecular and genetic advances have enabled a greater fidelity in classification of osteopetrosis subtypes. In the more severe ARO forms (e.g., malignant infantile osteopetrosis MIOP) typical clinical features have severe consequences and often result in death in early childhood. Major complications of ADO are atypical fractures with delay or failure of repair and challenge in orthopedic management. Bone marrow failure, dental abscess, deafness and visual loss are often underestimated and neglected in relation with lack of awareness and expertise. Accordingly, the care of adult patients with osteopetrosis requires a multidisciplinary approach ideally in specialized centers. Apart from hematopoietic stem cell transplantation in certain infantile forms, the treatment of patients with osteopetrosis, has not been standardized and remains supportive. Further clinical studies are needed to improve our knowledge of the natural history, optimum management and impact of osteopetrosis on the lives of patients living with the disorder.

OBJECTIVE: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women.
METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity.
RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant.
CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.