Oral microbiota dysbiosis, particularly in periodontitis, represents a significant yet under-recognized contributor to systemic bone loss and heightened osteoporosis risk. Disruption of the symbiotic oral microbial community permits pathobiont expansion, notably Porphyromonas gingivalis triggering chronic gingival inflammation. This local inflammatory milieu drives alveolar bone resorption through receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis and matrix metalloproteinase activation. Notably, these pathological processes extend beyond the oral cavity by three interconnected mechanisms of hematogenous dissemination of periodontal pathogens and their virulence factors, which directly stimulate osteoclast differentiation in distant skeletal sites and by systemic spillover of pro-inflammatory cytokines, amplifying bone-resorptive signaling throughout the skeleton, across with dysregulation of the gut-bone axis, as oral pathobionts translocate to the gastrointestinal tract, altering gut permeability and microbiome composition to further exacerbate inflammatory bone loss. Epidemiological studies consistently associate periodontitis with reduced bone mineral density and increased fracture incidence, independent of traditional osteoporosis risk factors. Animal models confirm that oral pathogen challenge accelerates trabecular bone loss in long bones and vertebrae. These findings position oral dysbiosis as a modifiable risk factor for osteoporosis, suggesting that periodontal therapy and microbiome-targeted interventions may offer adjunctive strategies for skeletal health preservation. Future research should prioritize longitudinal human studies to establish causality and evaluate whether periodontal treatment attenuates systemic bone loss trajectories in at-risk populations.
Maternal primary hyperparathyroidism (PHPT), though rare during pregnancy, poses significant and disproportionate risks to the fetus and newborn due to transplacental passage of maternal calcium and parathyroid hormone (PTH). This condition disrupts the fetal mineral regulatory milieu, establishing a critical pathophysiological sequence. Sustained maternal hypercalcemia directly suppresses the development and function of the fetal parathyroid glands in utero, inducing a state of functional dependence on the maternal hypercalcemic environment for calcium homeostasis. Consequently, at delivery, the abrupt termination of both the maternal hypercalcemic drive and placental calcium transfer precipitates a high-risk period for the neonate. The infant, born with profoundly suppressed parathyroid reserve, faces a substantial challenge in mounting an adequate PTH secretory response to the sudden drop in calcium supply. This pathophysiological lag universally triggers neonatal hypocalcemia, the severity and duration of which are intrinsically linked to the depth and chronicity of in utero parathyroid suppression, as well as the individual neonate’s capacity for parathyroid functional recovery. Clinical manifestations can range from asymptomatic biochemical hypocalcemia to severe, life-threatening complications including seizures, tetany, apnea, and cardiomyopathy. Understanding this mechanistic pathway, from maternal hypercalcemia to fetal gland suppression and the predictable postnatal hypocalcemic crisis is paramount. It underscores the necessity for vigilant prenatal diagnosis of maternal PHPT, meticulous intrapartum planning, and intensive, protocol-driven neonatal monitoring and calcium/active vitamin D replacement strategies to prevent significant neonatal morbidity. Early recognition of this iatrogenic dependence is crucial for optimizing outcomes in affected offspring.
Pediatric obesity is characterized by a bidirectional metabolic dysregulation of vitamin D metabolism within adipose tissue, creating a state of functional deficiency that standard serum measurements often underestimate. Expanded adipose mass acts as a volumetric sink, sequestering fat-soluble vitamin D metabolites and contributing to low circulating 25-hydroxyvitamin D levels, inversely correlated with body fat. Crucially, adipose tissue inflammation drives profound local metabolic disruption, where pro-inflammatory cytokines (TNF-α, IL-6) down-regulate the activating enzyme CYP27B1 (1α-hydroxylase) and upregulate the degrading enzyme CYP24A1 (24-hydroxylase) in adipocytes and macrophages. This ‘double hit’ severely diminishes 1,25-dihydroxyvitamin D [1,25(OH)2D] within the adipose microenvironment, impairing vitamin D receptor (VDR) signaling precisely where it is needed to suppress inflammation. Systemic inflammation further compromises vitamin D status by reducing hepatic CYP2R1 activity, limiting the conversion of vitamin D to 25(OH) D. Additionally, obesity-associated alterations in vitamin D-binding protein (DBP) levels and isoforms may reduce the bioavailable (free) fraction of vitamin D metabolites, exacerbating tissue-level deficiency despite potentially borderline total serum 25(OH)D. Consequently, the combination of sequestration, inflammation-induced dysregulation of activating/degrading enzymes, and altered binding protein dynamics creates a significant disconnect, where standard serum 25(OH)D levels fail to reflect the critical local deficiency of bioactive vitamin D within the inflamed adipose tissue of obese children. This tissue-specific functional deficiency, driven by inflammation, underpins the impaired immunomodulation and perpetuates metabolic dysfunction, highlighting the inadequacy of conventional vitamin D assessment in obesity and necessitating consideration of bioavailability and tissue metabolism.
Recent findings detected a dynamic, reciprocal relationship between bone remodeling and cardiac dysfunction, significantly influencing atherosclerosis pathogenesis. The bone-heart axis consists of bidirectional signaling of bone-derived factors and dysregulated mineral metabolism, which directly affect vascular calcification, endothelial function, and myocardial stress. Conversely, cardiac hormones and systemic inflammation modulate osteoclast/osteoblast activity. Critically, shared molecular pathways, like RANKL/RANK/OPG modulate both skeletal turnover and vascular inflammation/calcification. Pathological bone resorption releases calcium and matrix vesicles that nucleate vascular calcification, accelerating atherosclerotic plaque instability. Reimagining this axis emphasizes on osteo-immunological mechanisms with central role in cardiovascular disease progression, suggesting integrated therapeutic targets for atherosclerosis beyond traditional lipid-centric approaches.
Primary hyperparathyroidism (PHPT), characterized by chronic parathyroid hormone (PTH) excess and sustained hypercalcemia, disrupts the oral environment by intricate systemic-oral interactions. Hypercalcemia alters salivary composition, viscoelasticity, and flow rate, impairing its antimicrobial properties while promoting bacterial adhesion and calcified plaque formation. These changes foster pathogenic microbial colonization and hasten dental calculus deposition. Concurrently, excess PTH directly triggers osteoclastic resorption in alveolar bone, amplifies proinflammatory cytokines, and boosts matrix metalloproteinases, culminating in periodontal destruction and dysbiosis. Clinically, patients experience heightened tooth mobility, accelerated periodontitis, increased caries risk, and oral discomfort. This oral dysbiosis-inflammation axis further elevates systemic inflammatory burden, exacerbating PHPT-related cardiovascular, metabolic, and renal comorbidities. The interplay between PTH-mediated endocrine dysregulation and oral microbiome shifts highlights the imperative for integrated care. Dentists serve as early detectors of subtle oral signs potentially unmasking undetected PHPT, while endocrinologists must incorporate routine dental assessments. Best results arise from collaborative strategies, including intensive preventive dentistry, meticulous oral hygiene, regular surveillance, and parathyroidectomy when warranted, to interrupt this vicious cycle and reestablish oral and systemic equilibrium.
A sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy promotes renal glucosuria, which triggers phosphaturia and initiates a cascade of metabolic and hormonal disturbances. The resulting hypophosphatemia stimulates secondary hyperparathyroidism, which in turn elevates fibroblast growth factor 23 (FGF23), further suppressing serum phosphate, calcitriol, and calcium levels. Concurrently, the osmotic diuresis and caloric loss induce a negative energy balance, shifting metabolism toward ketogenesis. Elevated β-hydroxybutyrate not only serves as an alternative fuel but also directly stimulates osteoclast activity while inhibiting osteoblast function. Compounding this, therapy-associated hypoinsulinemia diminishes anabolic signaling through insulin and insulin-like growth factor-1 (IGF-1), both critical for bone formation. At the heart of this skeletal disruption lies osteocyte dysfunction. Hypophosphatemia and altered hormonal milieu—particularly increased PTH and FGF23 upregulate sclerostin, a potent inhibitor of the Wnt/β-catenin pathway, thereby suppressing bone formation. Furthermore, alterations in adipokines following weight loss further modulate bone metabolism. Critically, these pathways interact synergistically: PTH enhances bone resorption and sclerostin production; FGF23 suppresses calcitriol, worsening hypocalcemia; and ketones amplify RANKL-driven osteoclastogenesis. Additionally, mechanical unloading from rapid weight loss independently increases sclerostin expression. The net effect is a profound uncoupling of bone remodeling, accelerated resorption driven by PTH, RANKL, ketones, and inflammatory cytokines, coupled with suppressed formation due to sclerostin, hypoinsulinemia, and direct ketone effects. Clinically, this manifests as rapid trabecular bone loss, deteriorated microarchitecture, and a markedly elevated fracture risk, particularly during the initial months of treatment. Therefore, SGLT2 inhibitors confer significant cardio-renal benefits; however, they may impose substantial skeletal trade-offs that warrant careful monitoring.
Oncologic skeletal fractures or pathologic fractures resulting from tumor-induced bone destruction represent a devastating complication of both primary bone cancers and metastatic disease, profoundly impairing patient quality of life and survival. Traditionally viewed as mechanical failures secondary to osteolytic or osteoblastic lesions, emerging paradigms now recognize these fractures as the culmination of complex, dynamic interactions between tumor cells and the bone microenvironment. Recent advances highlight the role of tumor-secreted factors, which dysregulate normal bone remodeling by takeover of osteoclast and osteoblast activity, leading to structural weakening long before radiographic changes appear. Moreover, the concept of the vicious cycle between tumor growth and bone resorption has been expanded to include immune modulation, angiogenesis, and neural signaling within the skeletal niche. Novel imaging modalities and biomechanical modeling now enable earlier detection of at-risk bone, while biomarkers offer promise for risk stratification. Therapeutically, beyond bisphosphonates and denosumab, emerging strategies target specific molecular pathways like TGF-β, Wnt, CXCR4 to disrupt tumor-bone crosstalk and preserve skeletal integrity. Additionally, prophylactic stabilization guided by fracture risk assessment tools is increasingly personalized. Meanwhile, prevention, rather than reaction, is becoming the cornerstone of management, emphasizing collaboration among oncologists, orthopedic surgeons, radiologists, and bone biologists.
Pyle’s disease (PD) is a rare inherited skeletal dysplasia. Approximately 35 cases have been reported worldwide. It is more frequently reported in adults. This skeletal dysplasia has distinct radiologic features, which are characterized by widening of the distal metaphysis of the femur and proximal tibia, cortical thinning, and osteoporosis. Regarding the rarity of PD and the importance of reporting its presentations, we aimed to report a 4-year-old boy focusing on its radiographic, laboratory, and genetic findings. In this case report, we present a 4-year-old boy from consanguineous parents brought to the pediatric orthopedic clinic for abnormal shape of lower extremities and difficulty walking when he was 3 years old. He was evaluated and finally diagnosed with PD using whole exome sequencing.
Introduction: Parathyroidectomy is the definitive treatment for primary hyperparathyroidism and enhances bone density; thus, this study aimed to investigate the association between parathyroidectomy and fracture risk in individuals with primary hyperparathyroidism. Materials and Methods: This meta-analysis and systematic review were conducted through simple and advanced searches in PubMed, Cochrane, Web of Science, ProQuest, and Google Scholar. The search was updated until June 25, 2023. Data were collected using SPSS version 19 and analyzed with STATA software version 14. Results: Eleven cohort studies totaling 97,388 patients with primary hyperparathyroidism who had parathyroidectomy were included in the meta-analysis. In individuals with primary hyperparathyroidism, parathyroidectomy decreased the fracture risk by 15% (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.74, 0.99) overall and by 22% (OR: 0.78; 95% CI: 0.76, 0.80) in patients aged 70 to 79 years; however, no notable association was found between parathyroidectomy and the fracture risk in patients aged 50 to 59 years (OR: 0.99; 95% CI: 0.55, 1.76) and 60 to 69 years (OR: 0.84; 95% CI: 0.69, 1.02); additionally, parathyroidectomy resulted in a 29% reduction in the fracture risk in the USA (OR: 0.71; 95% CI: 0.61, 0.81) and a 23% reduction in the hip fracture risk (OR: 0.77; 95% CI: 0.60, 0.97); however, no statistically notable correlation was found between parathyroidectomy and the risk of hand, foot, vertebral, femur, forearm, spine, upper extremity, femoral neck, and osteoporotic fractures. Conclusion: Parathyroidectomy reduced fracture risk by 15%, notably preventing bone and hip fractures in people over 70. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (ID: CRD42024564707) and Research Registry (UIN: reviewregistry1854 websites.
Introduction: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are drugs administered to treat type 2 diabetes mellitus; however, their relationship with thyroid cancer is still unclear. Hence, the present study aimed to examine the association between the use of GLP1-RA and thyroid carcinoma. Materials and Methods: Databases searched—including Web of Science, Cochrane, Scopus, ProQuest, PubMed, Embase, and Google Scholar—were searched without a time limit until May 1, 2025. Data were entered into SPSS 19 and analyzed using STATA 14. Tests with P values less than 0.05 were considered statistically significant (P < 0.05). Results: The relationship between GLP1-RA and thyroid carcinoma based on hazard ratio (HR: 1.14, 95% CI: 0.86, 1.51) and incidence rate ratio (IRR: 1.32, 95% CI: 0.79, 2.20) was statistically insignificant. However, according to odds ratio (OR), use of GLP1-RA increased the risk of thyroid cancer (OR: 1.46, 95% CI: 1.23, 1.74). Furthermore, the association between GLP1-RA and medullary thyroid carcinoma was insignificant (HR: 1.51, 95% CI: 0.90, 2.54). The relationship between GLP1-RA and thyroid carcinoma among women (HR: 1.01, 95% CI: 0.69, 1.47), men (HR: 0.72, 95% CI: 0.33, 1.57), individuals aged 50 to 59 (HR: 1.30, 95% CI: 0.96, 1.75), 60 to 69 (HR: 0.95, 95% CI: 0.65, 1.38), in China (HR: 1.26, 95% CI: 0.91, 1.76), France (HR: 3.43, 95% CI: 1.30, 9.04), and Korea (HR: 1.05, 95% CI: 0.76, 1.46) was statistically insignificant. However, in the USA (HR: 1.44, 95% CI: 1.22, 1.71), GLP1-RA administration increased the risk of thyroid neoplasm. Conclusion: Generally, the relationship between the GLP1-RA use in patients with type 2 diabetes mellitus and the risk of thyroid carcinoma was insignificant. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (ID: CRD420251051827) and Research Registry (reviewregistry1993) websites.
Since evidence suggesting a direct link between mobile phone radiation and thyroid cancer is not conclusive, emerging studies indicate its biological effects on thyroid function among heavy users. The impact of mobile radiation on pediatric thyroid health warrants serious consideration as mobile technology becomes increasingly pervasive in children’s lives. The unique anatomical and physiological vulnerabilities present in children make them particularly susceptible to potential adverse effects from radio frequency electromagnetic radiation. Studies indicate a possible association between mobile radiation exposure and thyroid dysfunction. The complexity of interactions between mobile radiation, individual genetic backgrounds, and persistent health outcomes still needs several studies.
Cigarette smoking represents a major lifestyle risk factor for bone loss and skeletal disorders, with complex etiological mechanisms consisting both direct tissue effects and systemic alterations. Recent evidence demonstrates that tobacco smoking triggers an intricate cascade of cellular and molecular events that disrupts the delicate balance of bone remodeling, finally leading to decreased bone mass and increased fracture risk.
Introduction: Vitamin D deficiency has been implicated as a potential risk factor for metabolic disorders, including diabetes mellitus and obesity. Understanding the association between serum vitamin D levels and these conditions could guide future preventive strategies. Objectives: This study aims to investigate the relationship between serum vitamin D concentrations and the presence of diabetes mellitus and obesity through a prospective case-control design. Patients and Methods: This prospective case-control study was conducted over three months in Misan province, Iraq, involving 60 women aged 30–40 years, divided equally into healthy controls, obese, and type 2 diabetic groups. Blood samples were collected on the 10th day of the menstrual cycle and analyzed for serum 25-hydroxyvitamin D using an automated immunoassay. The study aimed primarily to compare vitamin D levels across the groups and secondarily to explore the relationship between vitamin D status and the presence of obesity and diabetes. Results: The comparative analysis of serum vitamin D levels among healthy individuals, obese individuals, and diabetes patients revealed a highly significant overall difference, with both the obese individuals and diabetic patients exhibiting notably lower vitamin D concentrations than healthy individuals. However, no significant difference was found between the vitamin D levels of obese and diabetic individuals, indicating comparable deficiencies in these metabolic disorder populations. Conclusion: The study identified a significant negative association between vitamin D concentration and both obesity and diabetes, highlighting the importance of targeted screening for metabolic disorders and vitamin D deficiency.
Introduction: Subclinical hypothyroidism (SCH) during pregnancy is a prevalent endocrine disorder, often managed with levothyroxine therapy. Although levothyroxine (LT4) is widely prescribed to mitigate potential risks associated with SCH, concerns persist regarding its safety profile and possible adverse effects on pregnancy outcomes. This systematic review evaluates the current evidence on the adverse maternal, fetal, and neonatal outcomes linked to levothyroxine use in pregnant women diagnosed with SCH. Materials and Methods: This systematic review was conducted on original research studies published between 2015 and 2025 that evaluated the adverse effects of levothyroxine use in pregnant women with SCH. Comprehensive searches were performed across PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Google Scholar. Data extraction was independently performed by two reviewers using a standardized checklist, with a third reviewer resolving any discrepancies. Results: The systematic review encompassed 12 studies totaling 1,952,592 participants (20,010 treated with LT4; 1,932,582 untreated). Preterm labor was the most frequent adverse outcome (reported in six studies), followed by gestational diabetes (three studies). Small-for-gestational-age (SGA) infants, low birth weight (LBW), and preeclampsia each appeared in two studies. Other effects, seizures in children, inadequate gestational weight gain, infant death, premature rupture of membranes, fetal macrosomia, and postpartum hemorrhage, were each noted once. Two studies found no adverse effects. Conclusion: This review study highlights preterm labor as the most common adverse outcome of LT4 use in pregnancy, followed by gestational diabetes. Repeated observations of SGA infants, LBW, and preeclampsia further highlight risks to fetal growth and maternal health. Less common but serious complications, such as seizures, inadequate weight gain, infant death, premature membrane rupture, fetal macrosomia, and postpartum hemorrhage, were each noted once, while two studies found no adverse effects, indicating that risk may depend on study factors, patient populations. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (ID: CRD420251105434) and Research Registry (UIN: reviewregistry2025) websites.
Introduction: Urinary tract infection (UTI) is among the most common bacterial infections in children, and evidently, it is associated with vitamin D deficiency. Accordingly, the present study intended to examine the frequency of vitamin D deficiency in children with UTI. Materials and Methods: Databases Scopus, PubMed, Embase, Web of Science, Cochrane, and Google Scholar Search Engine were used for articles published until August 1, 2025. Data was analyzed using STATA 14. Tests with P values <0.05 were considered statistically significant. Results: The frequency of vitamin D deficiency in the total population of children with UTI was, in case-control studies, and in cohort studies were 42%, 44%, and 38%, respectively. Furthermore, the rates of vitamin D deficiency in children with UTI aged under 3 years, those aged 3 to 5 years, and children older than 5 years were 21%, 46%, and 71%, respectively. Additionally, vitamin D insufficiency frequency in the total population of children with UTI, in case-control studies, and cross-sectional studies was 30%, 34%, and 22%, respectively. Moreover, the rates of vitamin D insufficiency in children with UTI aged under 3 years and those aged 3 to 5 years were 30% and 33%, respectively. Vitamin D deficiency was observed in 60% of the girls and 42% of the boys with UTI. Approximately 47% of the Asian and 20% of the European children with UTI suffered from vitamin D deficiency, and the frequency of vitamin D insufficiency in Asian and European children with UTI was 34% and 24%, respectively. Conclusion: Approximately half of the children with UTI suffered from vitamin D deficiency, and one-third of them faced vitamin D insufficiency. The increase in the age of the children added to the percentage of children with vitamin D deficiency or insufficiency. Furthermore, Asian children were at higher risk compared with European children, and females were exposed to higher risks than males. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (ID: CRD420251122224) and Research Registry (UIN: reviewregistry2033) websites.
Cancer-related bone metastasis represents a dynamic and multifaceted process driven by reciprocal interactions between malignant cells and the specialized bone microenvironment. Within this setting, the immune system exerts a pivotal influence, modulating both the progression of metastasis and the remodeling of bone tissue. The metastatic bone niche is frequently characterized by a state of immune dysregulation, in which chronic inflammation and immunosuppressive signaling pathways coexist. This interplay results in an environment that impairs effective antitumor immunity while simultaneously facilitating tumor cell colonization, survival, and osteolytic activity. A defining feature of bone metastasis is its tendency to establish an immunologically cold microenvironment, typified by low infiltration of cytotoxic T cells and reduced expression of immune-activating cytokines. However, this does not imply an absence of immune activity. Rather, certain immune cell subsets, such as regulatory T cells, myeloid-derived suppressor cells (MDSCs), and alternatively activated macrophages, accumulate within the metastatic site, where they secrete factors that suppress adaptive immune responses and support tumor-associated osteoclast activation. Through these mechanisms, cancer cells effectively hijack immune regulatory pathways to evade immune surveillance and promote bone destruction. On the other hand, systemic inflammation and cytokine storms are central players in the complex network governing bone metastatic progression. They create a pro-tumor, osteolytic environment by recruiting immunosuppressive cells, fueling osteoclast activity, promoting tumor cell survival and dissemination, and destabilizing the bone matrix. These inflammatory processes are intertwined with immune evasion mechanisms, tissue remodeling, and dormancy-reactivation cycles, collectively accelerating the metastatic cascade in bone. Targeting these inflammatory pathways represents a critical strategy to alter the course of metastatic disease and improve therapeutic outcomes.
The brain-gut-bone axis plays a crucial and complex role in regulating bone metabolism, particularly in the context of osteoporosis. This multidirectional communication network integrates signals from several physiological systems, including the gut microbiota, immune system, nervous system, and hormonal environment, all of which collectively influence the balance between bone formation by osteoblasts and bone resorption by osteoclasts. The gut microbiota contributes to this axis by producing metabolites such as short-chain fatty acids (SCFAs) and modulating systemic inflammation, which in turn can affect bone cell activity and mineralization processes. The immune system participates through cytokine signaling that either promotes or inhibits bone resorption and formation, linking inflammation to bone health. Meanwhile, the nervous system, via autonomic and sensory pathways, regulates nutrient absorption, bone blood flow, and directly modulates bone cell function through neuropeptides and neurotransmitters. Hormonal factors, including parathyroid hormone, sex steroids, and gut-derived hormones like serotonin, further modulate bone turnover by fine-tuning osteoblast and osteoclast activity. Disruptions in any component of this axis, such as dysbiosis of the gut microbiota, chronic inflammation, neurotransmitter imbalance, or hormonal deficiencies can lead to dysregulated bone remodeling, favoring increased bone resorption, decreased bone formation, and eventually decreased bone density. This manifests clinically as osteoporosis, characterized by fragile bones and elevated fracture risk. Therefore, understanding and targeting the brain-gut-bone axis presents promising therapeutic opportunities. Interventions such as probiotics, anti-inflammatory therapies, neuromodulation, and hormone replacement can potentially restore the balance in this axis, improving bone health and reducing osteoporosis progression. This integrative approach highlights the importance of systemic interactions and opens new avenues for precision medicine in bone metabolic disorders.
The parathyroid-leptin axis represents a network of hormonal interactions that play a critical role in regulating calcium homeostasis, energy balance, and metabolic health. The parathyroid hormone, primarily responsible for maintaining calcium and phosphate balance, interacts intricately with leptin, a hormone secreted by adipose tissue that regulates appetite, energy expenditure, and bone metabolism. This interplay involves both direct and indirect mechanisms, including leptin’s influence on parathormone (PTH) secretion and PTH’s modulation of leptin signaling in adipose tissue. Calcium and vitamin D further fine-tune this axis, creating a feedback loop that integrates bone, adipose, and metabolic functions. Dysregulation of the parathyroid-leptin axis has been implicated in various pathological conditions, such as osteoporosis, obesity, and metabolic disorders, highlighting its significance in maintaining physiological homeostasis. This review explores the mechanisms underlying the parathyroid-leptin axis, its physiological and pathological implications, and its potential as a therapeutic target for metabolic and bone-related diseases.
Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by the overproduction of parathyroid hormone (PTH), leading to disrupted calcium metabolism and hypercalcemia. Previously, PHPT was recognized as a symptomatic disease with severe skeletal, renal and neuromuscular manifestations. However, the advent of routine calcium screening has shifted the clinical profile toward milder, often asymptomatic presentations, particularly in developed countries. Despite this evolution, significant global disparities persist in the prevalence, clinical presentation and management of PHPT. In developing regions, symptomatic cases with advanced complications remain prevalent, driven by limited access to diagnostic resources, nutritional deficiencies and genetic factors. Exploring the evolving clinical profiles of this disease from a global perspective emphasizes regional variations in epidemiology, etiology and treatment approaches, examines the impact of socioeconomic, environmental, and genetic factors on the disease’s presentation and outcomes and addresses the challenges of diagnosis and management in resource-limited settings.
Paget’s disease of bone (PDB) is an osteopathy that progressively affects one or multiple bones, often involving the neurological system. The disease can impact the spinal cord, cauda equina, brain, and cranial nerves due to their proximity to affected bones. The involvement of the cranial nerve may lead to vision, hearing or speech loss. Radiological identification includes features like hypertrophic bones and cortical thickening. Neurological symptoms such as headaches, dementia, cranial neuropathies, and spinal issues may arise, though many cases are asymptomatic and discovered incidentally. The skull is frequently involved, leading to abnormal bone growth. Neurological deficits are often caused by spinal hypertrophy, direct compression, or pathologic fractures. Diagnostic tools like magnetic resonance imaging (MRI), CT-myelography, and bone X-rays are essential for locating lesions and guiding treatment. Treatment varies based on the severity and progression of the neurologic deficit, with bisphosphonates commonly used for progressive or chronic cases.
