Nutrition plays a critical role in maintaining bone health and excessive secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), in patients with acromegaly has been associated with disrupting bone remodeling and increased risk of vertebral fractures. The aim of this study was to assess the dietary quality of patients with acromegaly and its impact on bone density, quality and fractures.

This is a cross-sectional, observational, controlled study which included individuals with acromegaly (AG) and matched controls by sex and age (CG). Food intake was evaluated by a food frequency questionnaire (FFQ) and dietary reference intakes (DRIs). Bone mineral density (BMD) and bone quality [trabecular bone score] (TBS) measured by dual-energy X-ray absorptiometry (DXA) and the history of past fractures captured by a questionnaire.

Eighty-two individuals were included, 41 in the AG (58.5 % women, mean age 55.9 ± 11.8 years; mean body mass index (BMI) 31.14 ± 5.16) and 41 in the CG (58.5 % women, 56.8 ± 14.3 years and mean BMI was 25.5 ± 3.3). The mean age at diagnosis of acromegaly was 43.7 ± 13.0 years and 63.4 % of AG had a controlled disease. In both groups, insufficient intake, compared to DRIs, of essential nutrients (fiber, omega-3 and 6, vitamins A and E) and minerals (magnesium, potassium, and calcium) was observed. Compared to the CG, the AG showed a higher intake of carbohydrates, trans fats, and certain micronutrients compared to the CG, p < 0.05 for all, similar BMD values, higher number of fractures (AG 0.63 ± 1.11 vs. CG 0.14 ± 0.43; p = 0.001) and poorer TBS (men AG 1.10 ± 0.43 vs. CG1.43 ± 0.09; p = 0.006; women AG 1.03 ± 0.54 vs. CG 1.35 ± 0.14; p = 0,009). In the AG fractures were negatively associated to flavones and vitamin A, and positively associated to IGF-1 levels (p < 0.05 for all). BMD and TBS were positively associated with different bioactive compounds (flavone, anthocyanin, beta-carotene and vitamin C), macronutrients and vitamins with anti-inflammatory activity.

individuals with acromegaly had low bone quality and higher prevalence of fractures despite adequate BMD associated to Inadequate intake of antioxidant and anti-inflammatory compounds, combined with excessive consumption of trans fats and poor-quality carbohydrate.

A young male patient presented with acute onset spastic quadriparesis. Clinically, he exhibited features of acromegaly alongside spastic quadriparesis. Neuroimaging revealed an osteophyte complex causing cord compression and canal stenosis. Biochemical and radiological assessments confirmed a growth hormone-secreting pituitary macroadenoma. He underwent anterior cervical discectomy with vertebral fusion of the cervical cord to relieve his neurological symptoms. His acromegaly was subsequently managed with surgery, followed by radiotherapy and medical therapy. While acromegaly may rarely present as a metabolic emergency, neurological emergencies are exceptionally rare. This is the first case report of acromegaly, which was recognised on presentation with an osteophyte complex causing quadriparesis.

Background: Stunting remains a significant global health issue, particularly in low- and middle-income countries (LMICs). Globally, around 22% of children under five are affected, with high rates persisting in South and Southeast Asia. This review examines government-led programs in high-performing LMICs (Nepal, Bangladesh, and Vietnam) to identify key strategies and opportunities for effective intervention. Methods: A literature search was conducted on PubMed using keywords and Medical Subject Heading terms, including "stunting", "child undernutrition", "malnutrition" and the names of the three specified countries. Articles were evaluated for relevance based on their focus on stunting prevalence, risk factors, and interventions in these countries, without restrictions on publication date or language. Results: Stunting prevalence among children under five has significantly declined in Nepal, Bangladesh, and Vietnam over the past two decades, reflecting the impact of sustained nutrition and health interventions. Nepal reduced stunting from 55.8% in 2000 to 26.7% in 2022, Bangladesh from 54.7% to 26.4%, and Vietnam from 41.5% to 19.3%. Successful strategies included multisectoral approaches integrating nutrition-specific and nutrition-sensitive interventions, enhanced policy frameworks, and strong governance. Despite progress, challenges remain, such as high wasting prevalence in Nepal and disparities among marginalized communities in Vietnam, emphasizing the need for targeted, context-specific interventions. Conclusions: Effective stunting reduction requires multisectoral strategies addressing underlying, intermediate, and immediate determinants. Insights from Nepal, Bangladesh, and Vietnam highlight the importance of sustained government commitment, robust policies, and coordinated interventions. Adapting these successful strategies to local contexts can support stunting prevention and management, promoting healthier and more resilient communities.

Background/Objectives: Immune cells are integral to bone homeostasis, including the repair and remodeling of bone tissue. Chronic dysregulation within this osteoimmune network can lead to bone marrow defects of the jaw (BMDJ), particularly fatty degenerative osteonecrosis of the jaw (FDOJ). These localized pathologies are implicated in systemic immune dysfunctions. Methods: This study is designed to determine whether BMDJ/FDOJ samples are indicative of medullary bone pathology by evaluating FDOJ gene expression patterns using quantitative real-time PCR. Results: Comparative analyses between pathological and healthy samples evaluated the dysregulation of key molecular pathways. BMDJ/FDOJ samples showed significant upregulation of inflammatory mediators, including CCL5/RANTES, VEGF, IGF and KOR, and downregulation of structural proteins, such as collagen types I, II and IV, and osteogenesis-associated factors, such as SP7. Conclusions: The study provides new insights into the molecular mechanisms of BMDJ/FDOJ by identifying potential molecular changes suggesting a pro-inflammatory state in the affected jawbone which may contribute to systemic immune dysregulation. The findings are consistent with morphologic observations of BMDJ/FDOJ in degenerated jawbone and underscore the need for integrative approaches in dentistry and medicine while highlighting BMDJ/FDOJ as a potential target for therapeutic and preventive strategies against systemic diseases and emphasizing its clinical significance.

Long-acting growth hormone (LAGH) has the potential to improve adherence and outcomes over daily somatropin in growth hormone deficiency (GHD). Whereas daily somatropin products are molecularly identical, LAGHs are molecularly distinct; additional moieties or mechanisms that prolong LAGH action confer unique pharmacodynamic/pharmacokinetic properties that could affect efficacy and safety. Only one LAGH available in the United States and Europe (lonapegsomatropin) delivers unmodified somatropin. With no head-to-head clinical trials of LAGHs available, this systematic literature review and network meta-analysis were conducted to compare the relative efficacy and safety of LAGHs in pediatric GHD. Five trials were eligible for inclusion in a Bayesian network meta-analysis; 3 contributed to the base case network, including 3 LAGHs (lonapegsomatropin, somapacitan, and somatrogon) and daily somatropin. Treatment with lonapegsomatropin was associated with statistically significantly higher annualized height velocity and change from baseline in height SD score (SDS) at week 52 compared to daily somatropin and somapacitan; no other significant differences in these outcomes were found. The change from baseline in average insulin-like growth factor-1 (IGF-1) SDS at week 52 was significantly higher for somatrogon vs all comparators and for lonapegsomatropin vs daily somatropin and somapacitan; average IGF-1 SDS was within normal range in all trials. No significant differences were seen in progression in bone age-to-chronological age ratio or serious adverse events (SAEs). Sensitivity analyses were consistent with the base case. In this network meta-analysis, lonapegsomatropin was the only LAGH associated with better growth outcomes. No significant differences were detected regarding SAEs; other safety outcomes could not be analyzed.

This research aims to explore the effects of incorporating Saccharomyces cerevisiae fermentation products (SCFP) on growth performance, nutrient digestibility, antioxidant capacity, fecal short-chain fatty acids, and microbial composition of pre-weaning calves.

Twenty Holstein calves, 10 days old and weighing an average of 48.63±0.91 kg, were randomly assigned to either the control group (CON) or the SCFP group, with 10 calves in each group. The CON group received only a basal diet, while the SCFP group received the starter diet supplemented with 5 g/head/d of SCFP products. The pre-trial period lasted for 5 days, followed by a main experimental period of 45 days.

The SCFP group had significantly higher final weight, average daily gain, and feed efficiency compared to the CON group (p<0.05). Moreover, the SCFP group exhibited increased apparent digestibility of dry matter, crude protein, ether extract, acid detergent fiber, Ca, and P (p<0.05). Additionally, supplementation with SCFP led to elevated content of growth hormone, insulin-like growth factor-1, and glucagon-like peptide-1 in serum. The inclusion of SCFP also raised serum catalase content and reduced serum malondialdehyde content in pre-weaning calves. Furthermore, SCFP supplementation influenced the composition of intestinal microflora by decreasing Actinobacteriota abundance and increasing the abundance of Ruminococcus, Lachnospiraceae_AC2044_group, Parabacteroides, and Butyricimonas.

The addition of SCFP has a positive impact on the growth performance, nutrient digestibility, antioxidant capacity, and intestinal microflora composition of pre-weaning calves.

Osteoporosis, a debilitating condition characterized by reduced bone mass and increased fracture risk, is notably influenced by estrogen deficiency and glucocorticoid treatment. This comprehensive review elucidates the molecular mechanisms underpinning estrogen deficiency-related osteoporosis (EDOP) and glucocorticoid-induced osteoporosis (GIOP). The role of estrogen in bone metabolism is critically examined, highlighting its regulatory effects on bone turnover and formation through various signaling pathways. Conversely, this review explores how glucocorticoids disrupt bone homeostasis, focusing on their impact on osteoclast and osteoblast function and the subsequent alteration of bone remodeling processes. The pathogenesis of both conditions is intertwined, with estrogen receptor signaling pathways and the role of inflammatory cytokines being pivotal in driving bone loss. A detailed analysis of pathogenetic and risk factors associated with EDOP and GIOP is presented, including lifestyle and genetic factors contributing to disease progression. Modern therapeutic approaches emphasize pharmacologic, non-pharmacologic, and herbal treatments for managing EDOP and GIOP. In summary, current therapeutic strategies highlight the efficacy and the safety of various interventions. This review concludes with future directions for research, suggesting a need for novel treatment modalities and a deeper understanding of the underlying mechanisms of osteoporosis. By addressing the multifaceted nature of EDOP and GIOP, this work aims to provide insights into developing targeted therapeutic strategies and improving patient outcomes in osteoporosis management.

Precise regulation of organ size and position is crucial for optimal organ function. Since the swim bladder is primarily responsible for buoyancy in teleosts, early development and subsequent inflation of the swim bladder should be appropriately controlled with the body growth. However, the underlying mechanism remains unclear. In this study, we show that the size and position of the swim bladder are physically constrained by the surrounding bones in zebrafish. Non-invasive micro-CT scanning revealed that the anterior edge of the swim bladder is largely attached to the os suspensorium, which is an ossicle extending medioventrally from the 4th centrum. Additionally, we observed that hoxc6a mutants, which lack the os suspensorium, exhibited an anterior projection of the swim bladder beyond the 4th vertebra. During the swim bladder development, we found that the counterclockwise rotation of the os suspensorium correlates with posterior regression of the swim bladder, suggesting that the os suspensorium pushes the swim bladder posteriorly into its proper position. Furthermore, our results revealed a close association between the posterior region of the swim bladder and the pleural ribs. In hoxaa cluster mutants with additional ribs, the swim bladder expanded posteriorly, accompanied by an enlarged body cavity. Taken together, our results demonstrate the importance of the surrounding bones in the robust regulation of swim bladder size and position in zebrafish.

The elderly are at a high risk of malnutrition as well as osteoporosis. In this review, we examined if the geriatric nutritional risk index (GNRI) can predict the risk of osteoporosis in the elderly.

In this PRISMA compliant systematic review we searched the electronic databases of PubMed, Embase, ScienceDirect, and Web of Science. The search included studies from inception of databases to December 29, 2023. All studies examining the association between GNRI and osteoporosis were included.

Seven studies were selected. All studies were cross-sectional in design. Meta-analysis of all seven studies showed that low GNRI was significantly associated with the risk of osteoporosis in elderly patients (OR: 1.33 95% CI: 1.15, 1.53). The interstudy heterogeneity was high as the I2 value was 87%. Results did not change on sensitivity analysis. Subgroup analysis based on study location, presence of diabetes, sample size, GNRI cut-off, method to determine cut-off, and diagnostic criteria for osteoporosis showed mixed results.

Low GNRI can be a simple marker for predicting osteoporosis in the elderly. Current evidence is from a few studies with a high risk of bias.

Probiotics have been demonstrated to enhance growth performance, immunity, and reproduction in aquaculture species. Probiotics are a strong candidate as new safe solution for antibacterial related antibiotic-resistant pathogenic bacteria. In this study, we conducted a 30-day feeding trial on 106 cfu/g of indigenous Gram-negative bacteria Shewanella algae A3 and Serratia marcescens Van80 UB3 as probiotics using post-larval shrimp at stage 10 (PL-10). The new isolate as a probiotic strain for shrimp aquaculture was establish for a safety profile of antibiotic resistance assessment using phenotypic and molecular approaches. The Pacific white shrimp (Litopenaeus vannamei) exhibited improved growth, enhanced digestive enzyme activities, normal histological structures, increased expression of growth-related genes, and improved immunity when fed diets containing either single or multi-indigenous probiotics. The multi-indigenous probiotic group (C) displayed significantly higher lipase, amylase, and protease activities (P < 0.01) compared to the other groups. Furthermore, growth performance in the multi-indigenous probiotic group (C) was significantly better than that in the single probiotic groups (P < 0.05). Additionally, the expression of growth-related genes, including IGF-1, ecdysteroid, and myosin in the intestines, hepatopancreas, and muscles, was significantly higher in group C (P < 0.05). These findings strongly suggest that enriching the diets of Pacific white shrimp with 106 cfu/g of multi-indigenous Gram-negative bacteria probiotics can significantly improve growth performance, immunity, contribute to sustainable shrimp farming practice, and reduce of antibiotics application in aquaculture.

Paediatric inflammatory bowel disease (IBD) is often complicated by bone loss resulting in an increased risk of fractures and impaired quality of life. Underlying inflammation, nutritional deficiencies and glucocorticoid therapy are some of the factors contributing to secondary osteoporosis in IBD. Optimising nutrition, dietary supplementation and timely screening are essential in preventing bone loss. Bisphosphonate therapy remains the cornerstone of medical management of osteoporosis. This review explores the various mechanisms contributing towards poor bone health in IBD and the recent advances in diagnostic and preventive approaches along with updates in management strategies.

Hepatic liver cirrhosis can lead to significant systemic complications, including the deterioration of bone health. The resulting bone complications can contribute to a decreased quality of life and increased healthcare burden. This study aimed to systematically review and analyze the risk of osteoporosis, fracture, and changes in bone mineral density (BMD) among patients with hepatic cirrhosis compared to non-cirrhotic healthy controls.

Adhering to PRISMA guidelines, studies were sourced from MEDLINE/PubMed, Scopus, Web of Science, and Embase up to July 2024, including observational studies that assessed osteoporosis, fracture, and BMD in cirrhotic versus non-cirrhotic patients. Meta-analyses were performed by calculating odds ratios (OR) and standardized mean differences (SMD) of outcomes. Sensitivity analyses and meta-regression were also conducted to explore the robustness and sources of heterogeneity.

The analysis included 21 studies with 76,521 cirrhotic and 695,330 control patients. Cirrhotic patients demonstrated significantly higher odds of osteoporosis (OR = 1.93 [1.84 to 2.03]). Fracture was notably elevated, with cirrhotic patients showing an OR of 2.30 [1.66 to 3.18]. Reductions in BMD were observed in both the lumbar spine (SMD = -0.57[-0.79 to -0.35]) and femoral neck (SMD = -0.41 [-0.71 to -0.12]). Sensitivity analyses confirmed these findings, and meta-regression highlighted that male prevalence impacted these associations in various ways.

Patients with hepatic cirrhosis are at heightened risk for osteoporosis and fractures, underlining the need for proactive screening and preventive strategies. Integrating cirrhosis into current fracture-risk models could enhance the assessment and management of bone health in these patients.

Mesenchymal stem cells (MSCs) are crucial for skeletal development, homeostasis, and repair, primarily through their differentiation into osteoblasts and other skeletal lineage cells. Key signaling pathways, including Wnt, TGF-β/BMP, PTH, Hedgehog, and IGF, act as critical regulators of MSC osteogenesis, playing pivotal roles in maintaining bone homeostasis and facilitating regeneration. These pathways interact in distinct ways at various stages of bone development, mineralization, and remodeling. This review provides an overview of the molecular mechanisms by which these pathways regulate MSC osteogenesis, their influence on bone tissue formation, and their implications in bone diseases and therapeutic strategies. Additionally, we explore the potential applications of these pathways in bone tissue engineering, with a particular focus on promoting the use of MSCs as seed cells for bone defect repair. Ultimately, this review aims to highlight potential avenues for advancing bone biology research, treating bone disorders, and enhancing regenerative medicine.

Osteosarcopenia is an emerging clinical condition highly prevalent in the older people. Affected subjects due to their intrinsic skeletal fragility and propensity to falls are at elevated risk of hip fractures which can increase morbidity and mortality. Strategies for attenuating the impact of predisposing factors on hip fractures are not yet well defined and should derive from multidisciplinary care and collaborations. Our aim was to narratively review available data on the preventive role of vitamin D and hip protectors on hip fractures in older patients with sarcopenia. Older subjects are at high risk of vitamin D deficiency and of falls due to several concomitant factors besides osteosarcopenia. Vitamin D protective actions against hip fractures may be mediated by both skeletal (increased mineralization) and extra-skeletal (reduced risk of falls) actions. Hip protectors may act downstream attenuating the effects of falls although their use is still not yet enough widespread due to the suboptimal compliance obtained by traditional hard devices. Concomitant use of vitamin D and hip protectors may represent an effective strategy in the prevention of hip fractures which need to be tested in ad hoc designed clinical trials.

Diet has been proven to have significant impacts on the pathogenesis and treatment of osteoporosis. This review attempts to elucidate the current progress and controversy surrounding the ketogenic diet (KD) and β-hydroxybutyrate (BHB) in osteoporosis and offers a novel perspective on the prevention and treatment of osteoporosis. The ketogenic diet has been broadly used in the treatment of epilepsy, diabetes, obesity, and certain neoplasms by triggering ketone bodies, mainly BHB. However, in most osteoporosis-related clinical and preclinical studies, the ketogenic diet has demonstrated the detrimental effects of inhibiting bone accumulation and damaging bone microarchitecture. In contrast, BHB is thought to ameliorate osteoporosis by promoting osteoblastogenesis and inhibiting osteoclastogenesis. The main purpose of this review is to summarize the current research progress and hope that more basic and clinical experiments will focus on the similarities and differences between ketogenic diet (KD) and BHB in osteoporosis.

Extra-label bisphosphonate (BP) use in juvenile horses is anecdotally reported, primarily for analgesic effects, despite the limited scientific understanding of biologic impacts on skeletally immature horses undergoing exercise. The objective of this study was to determine the effects of clodronate disodium (CD), a form of BP, on endocrine regulators of calcium. Thus, 32 yearling Quarter Horses were stratified by age (500 ± 13 d), body weight (BW; 336 ± 26 kg), sex (n = 16 geldings, n = 16 fillies), and initial bone optical density into 1 of 4 treatment groups for a 168-d trial. The experimental period was divided into 2 exercise phases to model industry standards. Investigators were blinded to treatment, and all horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW CD (OSPHOS) or saline (placebo) on days 0, 42, 84, and 126. Treatments consisted of control (CON; n = 8), 1-dose (1X; n = 8; day 84), 2-dose (2X; n = 8; day 0, 84), and 4-dose groups (4X; n = 8; days 0, 42, 84, 126). Serum samples were collected, and physical measurements were recorded including BW, wither height, hip height, body length, and heart girth circumference (HG) every 42 d, prior to treatment administration. Serum samples were analyzed for growth hormone (GH), calcitonin, parathyroid hormone (PTH), and ionized calcium (Ca2+). Data were analyzed using MIXED and CORR procedures of SAS. All physical measurements increased over time (P ≤ 0.01) but were not affected by treatment (P ≥ 0.62). Similarly, there was no effect of treatment for GH (P = 0.44), but concentrations tended to decrease over time (P = 0.09). A treatment × day interaction was observed for PTH (P = 0.05) where concentrations increased following a second CD dose. Specifically, concentrations increased on day 84 in 4X and on day 126 in 2X following the second treatment with CD whereas 1X and CON remained unchanged. Despite the increase in PTH, there was no effect on calcitonin (P ≥ 0.33). Ionized calcium concentrations decreased over time (P < 0.01) with no effect of treatment (P = 0.26). Parathyroid hormone was negatively correlated with serum Ca2+ (r = -0.28, P < 0.01), whereas calcitonin was not correlated with serum Ca2+ (r = 0.06, P = 0.48) nor PTH (r = -0.13, P = 0.12). According to these results, CD has no effect on growth morphometrics, but its use transiently increases PTH concentrations after 2 doses.

This study examined how isoflavone interventions impact bone health in postmenopausal women. Analyzing 73 trials found that isoflavones reduce bone resorption markers, enhance bone minerals, and increase hormones regulating bone metabolism. This suggests that isoflavones could help address bone health issues in postmenopausal women.

This study aimed to assess the impact of isoflavone interventions on bone turnover markers and various biochemical markers of bone metabolism through systematic review and meta-analysis.

Four electronic databases, including PubMed, Embase, Scopus, and Cochrane Library, were searched in September 2023 for investigating the effects of isoflavones on bone turnover markers as well as signaling molecules regulating osteoclast differentiation, bone minerals, and hormones regulating bone metabolism in postmenopausal women. The main effect estimates, obtained using a random-effects model, were summarized using the mean difference (MD) or standardized mean difference (SMD), as appropriate.

A total of 73 randomized controlled trials were included, comparing an isoflavone intervention to a placebo. Our findings demonstrated that isoflavone interventions significantly reduced bone resorption markers, that is, β cross-linked C-telopeptide of type 1 collagen (β-CrossLaps) (MD = - 0.0943 ng/mL; P = 0.0071) and pyridinoline (PYD) (SMD = - 0.9111; P = 0.0247). Moreover, isoflavone interventions positively affected bone mineral parameters by increasing serum calcium levels (MD = 0.3430 mg/dL; P = 0.0267) and decreasing serum phosphorus levels (MD = - 0.0648 mg/dL; P = 0.0435). Hormones involved in regulating bone metabolism, particularly insulin-like growth factor type 1 (IGF-1), exhibited significant increases following isoflavone interventions (MD = 9.8163 ng/mL; P < 0.0001). Subgroup analysis suggested that the effects of isoflavones on bone turnover markers are influenced by factors such as the duration since menopause and the intervention duration.

This systematic review and meta-analysis highlight the potential of isoflavone interventions to rectify imbalances in bone remodeling, enhance bone mineral homeostasis, and optimize hormones regulating bone metabolism in postmenopausal women.

Senile osteoporosis (SOP) is a multifactorial, age-related progressive phenomenon with a considerable morbidity and mortality. IGF-1 is an important regulator of bone reconstruction and metabolism throughout life. Nevertheless, our previous study unexpectedly found there is no change in the peak bone mass with a altered IGF-1 gene expression leaded by IGF-1 c.258 A > G synonymous mutation. Considering its involvement in the cellular senescence, we suspected c.258 A > G may participate in SOP. Therefore, the effect of IGF-1 c.258 A > G on SOP was firstly detected, the changes of bone formation and bone resorption index in SOP mice with two genotypes indicated it improved SOP. Then, the in vitro study confirmed the mutation ameliorates SOP by promoting the growth and development of senescent osteoblasts. At last, co-culture of osteoblast and osteoclast further verified the mutation prevents SOP by increasing the bone formation capacity of senescent osteoblasts. Collectively, this study illuminated the role of IGF-1 c.258 A > G in ameliorating SOP.

Pituitary hormones play a crucial role in regulating skeletal physiology, and skeletal fragility is a frequent complication of pituitary diseases. The ability to predict the risk of fracture events is crucial for guiding therapeutic decisions; however, in patients with pituitary diseases, fracture risk estimation is particularly challenging. Compared to primary osteoporosis, the evaluation of bone mineral density by dual X-ray absorptiometry is much less informative about fracture risk. Moreover, the reliability of standard fracture risk calculators does not have strong validations in this setting. Morphometric vertebral assessment is currently the cornerstone in the assessment of skeletal fragility in patients with pituitary diseases, as prevalent fractures remain the strongest predictor of future fracture events. In recent years, new tools for evaluating bone quality have shown promising results in assessing bone impairment in patients with pituitary diseases, but most available data are cross-sectional, and evidence regarding the prediction of incident fractures is still scarce. Of note, apart from measures of bone density and bone quality, the estimation of fracture risk in the context of pituitary hyperfunction or hypofunction cannot ignore the evaluation of factors related to the underlying disease, such as its severity and duration, as well as the specific therapies implemented for its treatment. Aim of this review is to provide an up-to-date overview of all major evidence regarding fracture risk prediction in patients with pituitary disease, highlighting the need for a tailored approach that critically integrates all clinical, biochemical, and instrumental data according to the specificities of each disease.

Bone health is often impaired in patients with hormone-secreting pituitary tumors. Since medical therapy is central to their care, understanding how its use impacts on this is highly important.

This review summarizes a systemmatic review of the literature on the effects of medical therapies for hormone-secreting pituitary tumors on bone.

In acromegaly, medical therapy lowers bone turnover marker (BTM) levels, consistent with correction of the high bone turnover of active disease, and overall, areal bone mineral density (aBMD) does not change or increases. Somatostatin-receptor ligand (SRL) and pegvisomant-treated acromegaly patients have persistently reduced volumetric BMD and microarchitectural abnormalities of the peripheral skeleton, deficits that are similar to those in surgically-treated patients. Fracture risk remains elevated in medically-treated acromegaly patients but in conjunction with biochemical control the risk is lessened. Treatment of prolactin-secreting tumors with dopamine agonists is associated with improvements in aBMD, but this does not always fully normalize despite effective medical treatment of the prolactinoma. In one cross-sectional study, prolactinoma patients had lower total volumetric BMD and impaired microarchitecture suggesting that bone microstructure does not fully normalize despite dopamine agonist therapy. Cross-sectional studies show a high rate of VF in patients with prolactin-secreting tumors that is lowered on cabergoline therapy, but still the fracture rate of men and postmenopausal women is higher than that of controls in some studies. Studies on the effects of modern-day medical therapy for Cushing's disease on bone are lacking.

More research is needed on the effectsof medical therapies for hormone secreting pituitary tumors on bone health.

Hypopituitarism is a rare but significant endocrine disorder characterized by the inadequate secretion of one or more pituitary hormones. The intricate relationship between hypopituitarism and bone health is a topic of growing interest in the medical community. In this review the authors explore associations between hypopituitarism and bone health, with specific examination of the impact of growth hormone deficiency, central hypogonadism, central hypocortisolism, and central hypothyroidism. Pathogenesis, diagnosis, and treatment options as well as challenges posed by osteopenia, osteoporosis, and fractures in hypopituitarism are discussed.

During osteogenesis, a large number of bioactive molecules, macromolecules, cells, and cellular signals are activated to induce bone growth and development. The activation of molecular pathways leads to the occurrence of cellular events, ultimately resulting in observable changes. Therefore, in the studies of bone tissue engineering and regenerative medicine, it is essential to target fundamental events to exploit the mechanisms involved in osteogenesis. In this context, signaling pathways are activated during osteogenesis and trigger the activation of numerous other processes involved in osteogenesis. Direct influence of signaling pathways should allow to manipulate the signaling pathways themselves and impact osteogenesis. A combination of sequential cascades takes place to drive the progression of osteogenesis. Also, the occurrence of these processes and, more generally, cellular and molecular processes related to osteogenesis necessitate the presence of transcription factors and their activity. The present review focuses on outlining several signaling pathways and transcription factors influencing the development of osteogenesis, and describes various methods of their manipulation to induce and enhance bone formation.

Active acromegaly may lead to irreversible complications. Among them, acromegaly osteopathy and fragility (vertebral and hip) fractures have emerged as frequent and precocious events in the natural history of the disease, being correlated with longer disease duration and higher growth hormone (GH) levels, accounting for patients' reported poor quality of life, physical performance and other life-impacting complications. Differently from primary osteoporosis, bone mineral density is not a reliable tool to predict fracture risk in this clinical setting, as patients with active disease frequently have normal or slightly reduced bone mass; whereas bone quality is particularly compromised, as determined by low trabecular bone score (TBS) in patients with active disease as compared to healthy controls or patients with cured/controlled disease. The evidence of impaired bone microstructure has been profoundly investigated with different computed tomography (CT) techniques, reporting low trabecular number and thickness as well as wide but more porous cortical bone, providing an explanation for such a high prevalence of vertebral fractures (up to 40-50% in selected cohorts). Since data on bone-active drugs are scanty, disease control remains a cornerstone to prevent fractures. Nonetheless, some potential protective effects may derive from vitamin D supplementation and pasireotide therapies, independently from disease status. Aim of this manuscript is to review the current and emerging evidence on skeletal fragility in patients with active and resistant acromegaly.

Growth hormone is fundamental for growth during childhood and for maintaining bone mass and homeostasis in the adults. GH deficiency causes decreased bone growth and osteopenia, whereas GH excess causes increased bone fragility and decreased bone quality. In the past, it was common knowledge that GH effects on the skeletal system were due to the production of IGF1 from the liver, which has a huge bone anabolic effect per se. However, with the progress of basic research techniques new light has been shed on the mechanisms underlying GH effect in bone, and it is now clear that GH has effects that go beyond the downstream activation of liver IGFs. Therefore, the purpose of this review is to summarize the milestones in basic research that led to the discovery of GH local activity on bone.

Prolactinomas account for more than half of pituitary adenomas, and besides their clinical impact on fertility and gonadal function, they lead to detrimental effects on bone. Patients with prolactinoma are prone to deterioration of bone structure caused not only by prolactin (PRL) induced hypogonadism but also by its direct actions on bone cells and calcium metabolism. However, clinical studies have shown inconsistent evidence regarding whether PRL could have a deleterious effect independently from gonadal insufficiency on skeletal integrity. Seminal studies from our group reported an increased prevalence of vertebral fractures (VFs) in both female and male patients with prolactinoma. Treatment of prolactinoma with dopamine agonists can restore gonadal function and improve bone mineral density. Since the presence of VFs may be related to more aggressive disease, bone comorbidities in prolactinoma should be managed by a multidisciplinary team in line with the recent concept of 'pituitary tumors centers of excellence'. The review aims to evaluate the mechanism of PRL actions on bone, as well as to provide practical indications for a modern approach to the management of skeletal complications of patients with prolactin-secreting adenoma considering different clinical characteristics and outcomes.

To further our understanding of the role of tumor necrosis factor (TNF)α on the inflammatory response in chondrocytes.

We explored the effects of TNFα on the transcriptome of epiphyseal chondrocytes from newborn C57BL/6 mice at the total and single cell (sc) resolution.

Gene set enrichment analysis of total RNA-Seq from TNFα-treated chondrocytes revealed enhanced response to biotic stimulus, defense and immune response and cytokine signaling and suppressed cartilage and skeletal morphogenesis and development. scRNA-Seq analyzed 14,239 ​cells and 24,320 genes and distinguished 16 ​cell clusters. The more prevalent ones were constituted by limb bud and chondrogenic cells and fibroblasts comprising ∼73 ​% of the cell population. Genes expressed by joint fibroblasts were detected in 5 clusters comprising ∼45 ​% of the cells isolated. Pseudotime trajectory finding revealed an association between fibroblast and chondrogenic clusters which was not modified by TNFα. TNFα decreased the total cells recovered by 18.5 ​% and the chondrogenic, limb bud and mesenchymal clusters by 32 ​%, 27 ​% and 7 ​%, respectively. TNFα had profound effects on the insulin-like growth factor (IGF) axis decreasing Igf1, Igf2 and Igfbp4 and inducing Igfbp3 and Igfbp5, explaining an inhibition of collagen biosynthesis, cartilage and skeletal morphogenesis. Ingenuity Pathway Analysis of scRNA-Seq data revealed that TNFα enhanced the osteoarthritis, rheumatoid arthritis, pathogen induced cytokine storm and interleukin 6 signaling pathways and suppressed fibroblast growth factor signaling.

Epiphyseal chondrocytes are constituted by diverse cell populations distinctly regulated by TNFα to promote inflammation and suppression of matrix biosynthesis and growth.

The regulation of growth hormone (GH) synthesis and secretion by somatotroph cells of the anterior pituitary is a highly complex process, mediated by a variety of neuroendocrine and peripheral influences. In particular, a key role is played by the hypothalamic peptides growth hormone-releasing hormone (GHRH) and somatostatin, which regulate the somatotroph axis with opposite actions, stimulating and inhibiting GH release, respectively. Since the discovery of GHRH about 50 years ago, many pathophysiological studies have explored the underlying intricate hormonal balance that regulates GHRH secretion and its interplay with the somatotroph axis. Various molecules and pathophysiological states have been shown to modulate the release of GH, GHRH, somatostatin and GH secretagogues. Collectively, the available evidence demonstrates how a vast number of neural and peripheral signals are conveyed and integrated to orchestrate a finely tuned response of the somatotroph axis that adapts to the body's varying needs for growth, metabolism, and repair. The present review aims to summarize the available evidence regarding the key regulators involved in the modulation of the somatotroph axis in humans, presenting detailed molecular insights on the signaling cascades at play. The interplay between different mechanisms governing somatotroph secretion is highlighted, underscoring the nuanced interdependence that maintains homeostasis and facilitates the body's ability to respond to internal and external stimuli.

A 30-day research was carried out to examine the impacts of dietary taurine (Tau) on ovaries maturation and physiological responses of Penaeus vannamei female brooders (29.4 ± 0.2 g). A basal diet (497 g kg-1 protein and 140 g kg-1 lipid) was administered with graded levels of Tau ranging from 0 (control) to 2, 4, 6, 8, and 10 g kg-1. A total of 180 shrimp brooders were stocked into 18 250 L black circular polyethylene tanks. Female (n = 5) and male (n = 5) shrimps were stocked in each tank and supplied with seawater (35.2 ± 3.1 g L-1 salinity, 28.9 ± 1.4°C) and the experimental feeds were offered to shrimp twice a day at 5% of their biomass. Supplementing diet with 4-8 g Tau kg-1 reduced latency period after eye stalk ablation to spawning (5-6 days) that was associated with higher hepatopancreatic and gonadosomatic (except for 8 g Tau kg-1 diet) indices (p < 0.05). With 10 g Tau kg-1 diet hepatopancreas glutathione peroxidase activity and total antioxidant capacity increased and catalase activity increased by 6 g Tau kg-1 diet. Supplementing diet with Tau-enhanced bile-salt dependent lipase activity in the gut. Docosahexaenoic acid and Tau levels were elevated in the ovaries with the increment of dietary Tau level (p < 0.05). Plasma total protein, calcium, cholesterol, and high-density lipoprotein increased with inclusion of 6-10 g Tau kg-1 diet. The transcription levels of vitellogenin, insulin-like growth factor II, superoxide dismutase, prophenoloxidase, and lysozyme genes transcription levels were upregulated in the hepatopancreas of shrimp brooders fed 6-10 g Tau kg-1 diet (p < 0.05). It seems that Tau at 4-8 g kg-1 diet by modulating lipid metabolism, antioxidant capacity, and immunocompetence can improve maturation and health status of P. vannamei brooders.

Despite a large number of observational studies examining the effect of coffee consumption(CC) on bone disorders(BDs), particularly, osteoarthritis(OA), osteoportic fracture(OF), and rheumatoid arthritis(RA), the conclusions are highly controversial. Thus, it is essential to examine the causal association between CC and BDs.

Mendelian randomization (MR) analysis was performed to assess the causal influence of CC on OF, RA, and OA. The main endpoint was the odds ratio (OR) of the inverse variance weighted (IVW) approach. In addition, the weighted median (WM), MR-Egger regressions, MR-pleiotropy residual sum and outlier (MR-PRESSO) and multivariable MR (MVMR) were included in sensitivity analyses. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks.

Primary MR analysis based on the IVW method suggested that changes in CC alter risk of OF (OR = 1.383, 95%CI 1.079-1.853, P = 0.039), RA(OR: 1.623, 95%CI 1.042-2.527, P = 0.032) and HOA (hip osteoarthritis, OR = 1.536, 95% CI 1.044-2.259, P = 0.021). However, these causal relationships were not robust in sensitivity analyses. In contrast, there is a positive causal relationship between increased CC and the risk of KOA (knee osteoarthritis, OR: 2.094, 95%CI: 1.592-2.754, P = 1.41 × 10-7), as evidenced by the IVW using random effect. A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy.

Based on our MR analysis, increased CC was causally linked to an increase in the risk of KOA. Genetic predictions suggested that CC reduction may have benefits for bone health.

Height gains result from longitudinal bone growth, which is largely dependent on chondrocyte differentiation and proliferation within the growth plates of long bones. The growth plate, that is, the epiphyseal plate, is divided into resting, proliferative, and hypertrophic zones according to chondrocyte characteristics. The differentiation potential of progenitor cells in the resting zone, continuous capacity for chondrocyte differentiation and proliferation within the proliferative zone, timely replacement by osteocytes, and calcification in the hypertrophic zone are the 3 main factors controlling longitudinal bone growth. Upon adequate longitudinal bone growth, growth plate senescence limits human body height. During growth plate senescence, progenitor cells within the resting zone are depleted, proliferative chondrocyte numbers decrease, and hypertrophic chondrocyte number and size decrease. After senescence, hypertrophic chondrocytes are replaced by osteocytes, the extracellular matrix is calcified and vascularized, the growth plate is closed, and longitudinal bone growth is complete. To date, gonadotropin-releasing hormone analogs, aromatase inhibitors, C-type natriuretic peptide analogs, and fibroblast growth factor receptor 3 inhibitors have been studied or used as therapeutic interventions to delay growth plate closure. Complex networks of cellular, genetic, paracrine, and endocrine signals are involved in growth plate closure. However, the detailed mechanisms of this process remain unclear. Further elucidation of these mechanisms will enable the development of new therapeutic modalities for the treatment of short stature, precocious puberty, and skeletal dysplasia.

The regeneration of osteochondral defects is challenging due to the complex structure of the osteochondral unit. This study aimed to develop a biomimetic scaffold by loading growth hormone (GH) and insulin-like growth factor-1 (IGF-1) into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and incorporating them into polycaprolactone (PCL) scaffolds to promote synchronized osteochondral regeneration. The nanoparticles were successfully immobilized onto PCL scaffolds pre-modified with polydopamine (PDA) to enhance cell adhesion and proliferation. The scaffolds exhibited a sustained release of GH and IGF-1 over 30 days. In vitro studies using rabbit adipose-derived stem cells (ADSCs) showed that the GH/IGF-1 nanoparticle-loaded scaffolds (PCL/PDA/M-PLGA) significantly promoted cell proliferation, chondrogenic differentiation, and osteogenic differentiation compared to control PCL/PDA scaffolds. In vivo experiments using a rabbit osteochondral defect model revealed that the PCL/PDA/M-PLGA scaffolds facilitated superior osteochondral regeneration, evidenced by increased subchondral bone formation and cartilage matrix deposition. Overall, this study demonstrates the potential of GH/IGF-1 nanoparticle-loaded PCL scaffolds for synchronized osteochondral regeneration and provides a promising strategy for treating osteochondral defects.

Due to rapid urbanization and industrialization, Cadmium (Cd) contamination is widespread. Meanwhile, the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. Cd is linked to bone damage. However, the osteotoxicity of environmental Cd exposure in NAFLD remains unclear. Therefore, this study aimed to investigate the effects and potential mechanisms of Cd on bone metabolism in NAFLD mice. NAFLD mice were treated with 50 mg/L cadmium chloride in drinking water for 12 weeks. Bone microstructures were scanned by Micro-CT. Liver lipid droplets and fibrosis were measured by histopathological staining. Insulin tolerance tests were performed in mice. RT-PCR and Western blot were performed to analyse hepatic inflammation factors. Results show no damage in healthy mice exposed to Cd. However, Cd exacerbated liver fibrosis and significantly reduced cancellous bone mineral density and decreased the number and thickness of trabecular bone in NAFLD mice. Additionally, the morphology of trabecular bone transformed from a plate structure to a rod structure in NAFLD mice after Cd exposure. The underlying mechanism appears to be related to the Cd-induced direct or indirect toxicity. Exacerbated liver fibrosis, increased inflammatory factors (TGF-β and IL-1β), and reduced lecithin-cholesterol acyltransferase (LCAT) and insulin-like growth factor-1 (IGF-1) might contribute to bone damages. Collectively, our study illustrates that despite lower dosing Cd exposure did not induce bone damages in healthy mice, Cd caused bone loss in NAFLD mice. Therefore, it is recommended that individuals with metabolic disorders should avoid working in Cd pollution environment and consuming cadmium-contaminated food and water.

Growth hormone (GH) plays a key role in human growth and development. In addition to promoting height growth, GH affects bone metabolism, bone size, and bone mineral density (BMD) in children and adolescents by affecting bone formation and resorption. Among them, the effect of GH on spinal growth has been widely concerned. Scoliosis is a three-dimensional structural spinal deformity characterized by lateral curvature of one or more segments of the spine accompanied by vertebral rotation and sagittal imbalance. For children with growth hormone deficiency (GHD), whether GH supplementation leads to scoliosis is still controversial. In recent years, numerous scholars have conducted extensive research to investigate the correlation between recombinant human GH replacement therapy and scoliosis, yielding divergent findings with some even presenting contradictory results. This study aims to investigate the impact of GH on spinal growth and explore the association between recombinant human GH replacement therapy and scoliosis by comprehensively reviewing the effects of GH and insulin-like growth factors 1 (IGF-1) on bone metabolism, bone mass, as well as examining the consequences of GHD on bone health. Additionally, we aim to access the influence of recombinant human GH replacement therapy on adolescent idiopathic scoliosis (AIS).

Secondary osteoporosis is associated with type 2 diabetes mellitus (T2DM), and there is conflicting evidence regarding the relationship between insulin-like growth factor-1 (IGF-1) and bone mineral density (BMD) in different populations. The objective of this study was to investigate the relationship between serum IGF-1 levels and BMD in patients with T2DM.

A retrospective cross-sectional study was performed on a cohort of 363 patients with T2DM, comprising men aged over 50 and women who are postmenopausal. Those with no significant medical history or medication affecting BMD or IGF-1 were considered. Data analyzed included IGF-1 levels, markers of bone metabolism, and measurements of BMD. To account for age and gender variations, we calculated IGF-1 standard deviation scores (IGF-1 SDS) for further investigation.

A significant increase in BMD at lumbar spine (LS), femoral neck (FN), and total hip (TH) was observed as IGF-1 SDS tertiles rose. We revealed a nonlinear correlation between IGF-1 SDS and BMD at these sites, with a common inflection point identified at an IGF-1 SDS level of -1.68. Additionally, our multivariate piecewise linear regression analysis highlighted a positive association between IGF-1 SDS and BMD at LS, FN, and TH when IGF-1 SDS exceeded the inflection point (β 0.02, 95% CI 0.01, 0.04 for LS; β 0.02, 95% CI 0.01, 0.03 for FN; β 0.02, 95% CI 0.01, 0.03 for TH). Conversely, below the inflection point, this association was not significant (β -0.04, 95% CI -0.10, 0.01 for LS; β -0.04, 95% CI -0.08, 0.01 for FN; β -0.03, 95% CI -0.08, 0.01 for TH).

These findings reveal a nonlinear relationship between IGF-1 SDS and BMD in T2DM patients. Higher serum IGF-1 levels were connected to increased bone density only after surpassing a certain threshold.

Ossification of the spinal ligament (OSL) is a spinal disorder characterized by abnormal bone formation in the spinal ligaments. Although clinical studies suggested that diabetes mellitus (DM) was associated with OSL, no consistent conclusion was drawn about the relationship between DM and the onset of OSL.

Studies with data on DM and OSL were retrieved by searching PubMed, Embase, Web of Science, and Cochrane Library from inception to August 23, 2023. Pooled estimates of odds ratios (ORs) with 95% confidence interval (95% CI) were calculated using random-effects models. Statistical analyses were performed by R 4.2.2 software.

A total of 17 studies with 70,945 participants were included. The quantitative findings demonstrated that a higher risk of DM was related to the onset of OSL (OR = 2.19, 95% CI: 1.27-3.79, p = 0.008). Subgroup analysis showed a higher rate of DM in OSL patients from Japan (OR = 3.29, 95% CI: 1.51-7.17, [Formula: see text] = 0.009) than from other regions. Moreover, patients with OSL had a higher rate of DM in age < = 60 group (OR = 3.46, 95% CI: 1.14-10.50, p = 0.035) than age > 60 group (OR = 2.26, 95% CI: 1.07-4.79, p = 0.036).

DM is significantly associated with an increased risk of developing OSL, especially in Japanese and people under 60 years old. Further studies with more participants were warranted to confirm the findings and provide new insights into the prevention and treatment of OSL.

The aim of this review article is to highlight the consequences of COGHD after the end of linear growth on bone mass and body composition and the opposing beneficial effects of continuing GH replacement in the transition period and young adults. The role of growth hormone in the period of late adolescence and young adulthood is well established, mainly in achieving peak bone mass and a favorable body composition, characterized by muscle mass increase and fat mass reduction. Patients with childhood onset growth hormone deficiency (COGHD), after reaching the adult height, have a reduced bone mineral density and muscle mass with increased fat mass compared to healthy controls. Inadequate body composition is a predictor for cardiovascular risk, while low bone mass in early youth hallmarks the risk of osteoporosis and bone fractures in later life. Cessation of growth hormone replacement (GHr) after completion of growth will lead to delayed peak bone mass and unbalanced body composition with increased abdominal fat deposits. According to numerous clinical studies monitoring the effects of GH treatment on the physical and psychological status of patients with persistent GHD after completion of growth, we suggest continuing this treatment between 16 and 25 years of age. It is advised that GHr in the transition period be administered in intermediate doses between those for the pediatric population and those for the adult population. Usual daily GHr doses are between 0.3 and 0.5 mg but need to be individually optimized, with the aim of maintaining IGF-I in the age-specific normal range.

Research on lean, energy-deficient athletic and military cohorts has broadened the concept of the Female Athlete Triad into the Relative Energy Deficiency in Sport (REDs) syndrome. REDs represents a spectrum of abnormalities induced by low energy availability (LEA), which serves as the underlying cause of all symptoms described within the REDs concept, affecting exercising populations of either biological sex. Both short- and long-term LEA, in conjunction with other moderating factors, may produce a multitude of maladaptive changes that impair various physiological systems and adversely affect health, well-being, and sport performance. Consequently, the comprehensive definition of REDs encompasses a broad spectrum of physiological sequelae and adverse clinical outcomes related to LEA, such as neuroendocrine, bone, immune, and hematological effects, ultimately resulting in compromised health and performance. In this review, we discuss the pathophysiology of REDs and associated disorders. We briefly examine current treatment recommendations for REDs, primarily focusing on nonpharmacological, behavioral, and lifestyle modifications that target its underlying cause-energy deficit. We also discuss treatment approaches aimed at managing symptoms, such as menstrual dysfunction and bone stress injuries, and explore potential novel treatments that target the underlying physiology, emphasizing the roles of leptin and the activin-follistatin-inhibin axis, the roles of which remain to be fully elucidated, in the pathophysiology and management of REDs. In the near future, novel therapies leveraging our emerging understanding of molecules and physiological axes underlying energy availability or lack thereof may restore LEA-related abnormalities, thus preventing and/or treating REDs-related health complications, such as stress fractures, and improving performance.

Endocrine regulation of bone metabolisms is the focus of the "Skeletal Endocrinology" series of meetings.

To report on the outcome of the discussion on the role of vitamin D/PTH axis in endocrine osteopathies held during the 10th Skeletal Endocrinology Meeting which took place in Stresa (Italy) in March 2023.

Vitamin D/PTH axis has relevant influence on several outcomes in the general population and in patients affected by endocrinopathies such as hypoparathyroidism and secreting pituitary adenomas.

Assessing the status of the vitamin D/PTH axis and using vitamin D and PTH as therapeutic agents is mandatory in several endocrine-related bone metabolic conditions.

Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies.

A longitudinal, retrospective, observational study was conducted on a cohort of 45 acromegalic patients not-responsive to first-generation somatostatin receptor ligands (fg-SRLs) and treated with GHR antagonist (Pegvisomant) or with the second-generation SRLs (Pasireotide long-acting release).

Second line treatments were Pegvisomant plus fg-SRLs in 26 patients and Pasireotide LAR in 19 patients. From the group treated with fg-SRLs+Peg-V, the fl-GHR isoform was identified in 18 patients (69.2%) and the d3-GHR isoform in 8 patients (30.8%). I-VFs arose exclusively in fl-GHR isoform carriers (p=0.039). From the group treated with Pasireotide LAR, the fl-GHR isoform was identified in 11 patients (57.9%), and the d3-GHR isoform in 8 patients (42.1%). I-VFs arose exclusively in d3-GHR isoform carriers (p=0.018). Patients with fl-GHR isoform had a higher risk for i-VFs if treated with fg-SRL+Peg-V (OR: 1.6 95%IC: 1.1-2.3, p=0.04), and a lower risk if treated with Pasi-LAR (OR: 0.26 IC95%: 0.11-0.66, p=0.038).

Our data support a predictive role of the GHR isoforms for the occurrence of i-VFs in acromegalic patients treated with second-line drugs, tailored to the individual patient. The knowledge of the GHR polymorphism may facilitate the choice of second-line therapies, improving the therapeutic approach, in the context of personalized medicine.

Gut microbiota plays an important role in the regulation of bone homeostasis and bone health. Recent studies showed that these effects could be mediated through microbial metabolites released by the microbiota like short-chain fatty acids, metabolism of endogenous molecules such as bile acids, or a complex interplay between microbiota, the endocrine system, and the immune system. Importantly, some studies showed a reciprocal relationship between the endocrine system and gut microbiota. For instance, postmenopausal estrogen deficiency could lead to dysbiosis of the gut microbiota, which could in turn affect various immune response and bone remodeling. In addition, evidence showed that shift in the indigenous gut microbiota caused by antibiotics treatment may also impact normal skeletal growth and maturation. In this mini-review, we describe recent findings on the role of microbiome in bone homeostasis, with a particular focus on molecular mechanisms and their interactions with the endocrine and immune system. We will also discuss the recent findings on estrogen deficiency and microbiota dysbiosis, and the clinical implications for the development of new therapeutic strategies for osteoporosis and other bone disorders.

Bone mineral density (BMD) impairment is one of the critical factors for long-term quality of life in adults growth hormone deficiency (AGHD). This study aims to investigate the annual changes in BMD in AGHD patients with different ages of onset and to identify predicting factors that influence BMD.

AGHD patients (n = 160) with available data for 4 years follow-up from a major tertiary medical center in China were retrospectively included (110 [68.8%] childhood-onset, 119 [74.4%] male). BMD of the axial bone (including total hip, neck of femur, and L1-4) derived from dual X-ray absorptiometry and final height were investigated at the first visit, 12 months, 24 months, 36 months, and 48 months thereafter. Low BMD was defined as Z-score ≤ -2.

The prevalence of low BMD was 30.0% at baseline and 12.5% at 4 years of follow-up. The CO AGHD group presented a significantly lower BMD than the AO AGHD group at the baseline (P = 0.009). In contrast, the CO AGHD group had significantly greater median annual BMD change than the AO AGHD group (0.044 vs. -0.0003 g/cm2/year in L1-4, P < 0.001), indicating a significant difference in the overall BMD trend between CO and AO groups. Childhood-onset (odds ratio [OR] 0.326, P = 0.012), low serum testosterone (OR 0.847; P = 0.004) and FT4 (OR 0.595; P = 0.039) level were independent risk factors for BMD loss.

The annual changes of BMD show a different pattern in AGHD patients with varying ages of onset. Patients with CO AGHD have a lower bone mass, and in general, appropriate replacement therapy is necessary for long-term bone health in AGHD patients.