Dual-energy X-ray absorptiometry (DXA) and FRAX remain the validated foundation of osteoporosis diagnosis and fracture-risk stratification, yet important gaps persist: treatment response on DXA is detectable only after eighteen to twenty-four months, risk within any FRAX category is heterogeneous, and the kinetics of therapy transitions are invisible on densitometry. Circulating biomarkers are candidate adjuncts to close these gaps. Serum C-terminal telopeptide of type I collagen (s-CTX) and procollagen type I N-terminal propeptide (s-P1NP), reaffirmed as reference markers by the 2025 IOF-IFCC consensus, reflect bone remodeling within weeks and can verify adherence, confirm on-target response and flag rebound resorption after denosumab discontinuation. Emerging analytes - sclerostin, RANKL/OPG, circulating microRNAs, proteomic and metabolomic panels, and polygenic risk scores - promise refinement of risk prediction and precision monitoring but are not yet ready for routine clinical use. This review critically examines the biological basis, analytical performance, clinical-trial evidence and practical application of bone biomarkers, positioning them as complements to, not replacements for, DXA and FRAX.

Clinical and research imaging have been instrumental in shifting our understanding of osteoarthritis from a structural, cartilage-focused disorder to a whole-joint complex disease with biomechanical and inflammatory components. Initially, the only osteoarthritis imaging modality was x-ray; therefore, the focal point of diagnosis was the bone: osteophytes, sclerosis, but most importantly, the joint space narrowing. Soft-tissue visualization, dynamic imaging, and advanced image analysis techniques have shown that numerous other joint tissues and features are associated with osteoarthritis progression and symptom severity, and many of them appear before joint space narrowing is detectable. Inflammatory features like bone marrow lesions and effusion-synovitis have emerged as promising targets for intervention. The exact pathogenesis of and structure-modifying treatments for osteoarthritis remain elusive. Clinical and research imaging modalities are essential tools for monitoring the initiation and progression of the disease, identifying targets for intervention, and quantifying the impact of new treatments.

Major guidelines recommend exercise for hip and knee osteoarthritis (OA), yet few provide guidance on how to prescribe it. This narrative review synthesizes high-quality and clinically relevant evidence on exercise therapy for hip or knee OA, prioritizing systematic reviews and randomized controlled trials. Findings were summarized across nine topics, with a focus on translating the evidence into specific guidance for clinicians. Clinicians should consider measuring pain, physical function, quality of life, and global assessment for most patients with hip or knee OA. When educating about OA, clinicians should focus on what patients can do and avoid impairment-based language. Exercise therapy is safe and provides small to moderate improvements in pain and function, although effects appear smaller for hip OA than for knee OA. No exercise type has proven superior, nor has a dose-response relationship been established. Patients with higher baseline pain and poorer function may benefit somewhat more, but effects differ little across other patient characteristics, including comorbidity burden and radiographic severity. Whether increasing adherence leads to greater improvements in pain and function remains unclear, but helping patients start and sustain exercise remains a priority, given its wide-ranging health benefits. In-person, telehealth, and self-directed delivery can all improve pain and function, and they appear to offer benefits of similar magnitude. Overall, exercise is safe, with the most common adverse event being temporary muscle or joint soreness. Clinicians do not need to search for an optimal program but can instead build one around the patient's priorities, preferences, and needs.

Osteoarthritis (OA) is a common condition affecting nearly 600 million people worldwide, resulting in significant morbidity and disability. This paper reviews the latest updates on the systemic and local risk factors associated with development and progression of this disease. Some systemic risk factors, such as increasing age and obesity for example, have been well-established as strong risk factors for decades. Other potential risk factors such as smoking, nutritional deficiencies, and various medication exposures are less well-understood currently and require further investigation. The review of local risk factors focuses on congenital and acquired abnormalities that contribute to OA development such as joint malalignment, leg length discrepancy, and prior injury among others. This overview of OA risk factors highlights the importance of identifying modifiable risk factors as targets for treatment and progression-prevention in patients with OA as well as for the purpose of risk stratification and prevention in unaffected individuals.

Artificial intelligence (AI) is increasingly influencing clinical care and research in osteoarthritis and osteoporosis. For patients, AI can broaden access to health information, including understanding of disease and treatment options. For clinicians, AI-based systems may assist risk stratification and decision-making, including identifying individuals most likely to benefit from specific therapies. In medical imaging, AI approaches can grade osteoarthritis severity, identify occult pathology (including atypical femoral fractures), and estimate low bone mineral density from non-dedicated examinations. In research, AI can facilitate analysis of complex, high-dimensional datasets (e.g., multi-omics and cell-cell communication) supporting the discovery of biomarkers, candidate therapeutic targets and disease endotypes. Emerging directions include agentic AI systems for end-to-end workflows, adaptation of foundation models pre-trained on large, diverse datasets, and carefully evaluated synthetic data for augmentation and validation/quality-control pipelines. This review examines current and emerging AI applications across osteoarthritis and osteoporosis, and pathways for safe, equitable and effective deployment.

Osteoporosis is increasingly recognized as a heterogeneous syndrome rather than a single disease, driven by diverse pathophysiological mechanisms. Subtypes-including postmenopausal estrogen deficiency, age-related bone loss, anorexia nervosa, and GLP-1 receptor agonist-associated weight loss-exhibit distinct bone turnover, fracture patterns, and therapeutic responses. Recent studies have established bone marrow adipose tissue (BMAT) as a critical regulator of the marrow microenvironment in postmenopausal and age-related bone loss. Weight loss of various origins-anorexia, GLP-1 agonists, caloric restriction, and intermittent fasting-impairs bone through reduced mechanical loading, hormonal alterations, IGF-1 resistance, adipokine dysregulation, and mesenchymal stem cell lineage shifts. Parathyroid hormone (PTH) shows bidirectional effects, with continuous exposure promoting resorption and intermittent stimulation enhancing formation, providing a rationale for subtype-guided therapy. Exercise exerts skeletal benefits via mechanical loading, myokines, autophagy, non-coding RNAs, and epigenetics, with effects varying by type and combination. This review synthesizes these mechanistic advances, differentiates the skeletal consequences of weight loss by etiology, and discusses the clinical application of PTH analogs, sclerostin antibodies, and tailored exercise prescriptions in personalized osteoporosis care.

Sarcopenia is a progressive skeletal muscle disorder characterised by reduced muscle strength, impaired muscle quantity or quality, and declining physical performance, with important consequences for falls, fractures, disability, and loss of independence. Whether sarcopenia prevalence itself is rising remains difficult to quantify because diagnostic frameworks and surveillance methods vary, yet a growing burden is plausible. Population ageing, increasing multimorbidity, obesity, hospitalisation, surgery, and incomplete recovery after musculoskeletal events are likely to increase the absolute number of people living with low musculoskeletal reserve. Osteoarthritis (OA) and osteoporosis (OP) are central to this problem because they amplify the functional consequences of weakness and reduced loading. OA may lead to strength loss through pain, inflammation, altered movement, and activity restriction, while OP increases the likelihood that falls or loading errors will result in fracture and subsequent deconditioning. Shared mechanisms for sarcopenia include mechanical unloading, adiposity-related metabolic dysfunction, inflammageing, mitochondrial stress, endocrine change, and nutritional insufficiency, although the strength of evidence differs across pathways. New weight-loss approaches using glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may substantially affect sarcopenia risk and therefore require careful consideration. Current diagnostic frameworks increasingly prioritise muscle strength and performance over lean mass alone, supporting pragmatic case-finding in older adults with severe OA, fragility fracture, recurrent falls, poor postoperative recovery, or weight loss. Current management should focus on progressive resistance and balance training, adequate energy and protein intake, guideline-based OP care, optimised OA treatment, and protection of mobility during transitions of care. The most immediate clinical gains are likely to come from integrating existing rheumatology, orthopaedic, fracture-prevention, rehabilitation, and nutritional services rather than from any osteosarcopenia-specific drug therapy.

Osteoporosis therapeutics have advanced from antiresorptive drugs that slow bone loss to osteoanabolic and dual-action agents that can rapidly rebuild skeletal integrity and reduce fracture risk. Yet the current anabolic era leaves important clinical questions unresolved: why responses vary among older adults, why gains are transient, how best to sequence therapy, and how to sustain skeletal resilience in the biologically aged bone microenvironment. Cellular senescence has emerged as a plausible mechanistic bridge linking skeletal aging, chronic inflammation, impaired osteoblastogenesis, increased osteoclastogenesis, marrow adiposity, diabetes-associated fragility, and delayed repair. Preclinical studies show that senescent-cell clearance can prevent or partially reverse age-related bone loss, while early human senolytic data suggest that skeletal response may depend on baseline senescent-cell burden. This review discusses current anabolic therapies, the rationale for senescence-targeted approaches, and future biomarker-informed strategies to integrate anabolic induction, antiresorptive consolidation, and experimental modulation of skeletal aging biology.

Osteoarthritis is a degenerative disorder of the whole joint and the leading cause of chronic disability in older adults, yet no disease-modifying therapy exists. Here we review what the gut microbiome teaches us about how osteoarthritis develops and progresses. We outline a biologically plausible gut-joint axis in which an altered intestinal community, a more permeable gut barrier, translocated microbial products, and low-grade systemic inflammation converge on the joint, together with the recently described bile acid and incretin changes. Animal experiments supply the strongest causal evidence, as removing, perturbing, or transplanting the microbiome alters joint damage. Human studies remain observational and often discordant, reflecting differences in the joint studied, in population, and in method; functional measures such as circulating endotoxin reproduce more reliably than taxonomic ones. We appraise therapeutic opportunities, including dietary fiber, prebiotics, weight loss, and incretin-based agents, and define the research agenda required before microbiome-directed therapy enters practice.

Psoriatic arthritis (PsA) is a chronic immune mediated musculoskeletal condition that is associated with psoriasis. PsA is recognized not as an isolated articular disorder, but as a systemic inflammatory condition with interrelated involvement of the skin, joints, entheses, spine, and gut. The systemic nature of PsA extends beyond musculoskeletal and cutaneous involvement to include a broad spectrum of comorbid and related inflammatory conditions that contribute to disease burden, treatment complexity, and long-term outcomes. PsA is associated with significant comorbidities. This includes cardiovascular disease, obesity, diabetes, fatigue and sleep disorders, mental health disorders and end-organ complications involving the kidney, liver, and bone, as well as related immune-mediated conditions such as inflammatory bowel disease and uveitis. This chapter examines the comorbidity landscape in PsA and underscores its importance in guiding more integrated and effective care. There is particular emphasis on multi-disciplinary evaluation to guide management. We will also explore the updated guidelines for screening, diagnostics, and treatment recommendations in addition to updates in the digital age.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, and up to half of patients continue to experience active disease or complications into adulthood. Despite this, adult rheumatology care remains largely oriented toward adult-onset disease, creating a mismatch in expertise for patients with childhood-onset arthritis. As a result, adult providers must address clinical challenges unique to childhood-onset disease, including persistent inflammation, temporomandibular joint (TMJ) involvement, long-term medication exposure, chronic pain, psychosocial morbidity, and extra-articular manifestations such as uveitis. Transition gaps are common and contribute to medication discontinuation, loss to follow-up, and disease flare. This review summarizes the long-term outcomes of JIA relevant to adult rheumatologists and outlines best practices in screening and management across key domains, including uveitis, TMJ arthritis, mental health, and educational and vocational participation. The review also highlights evidence-based practical strategies for building transition-informed adult rheumatology practices.

Fatigue is a common, debilitating, and challenging symptom in rheumatic diseases. Despite its clinical significance, the concept of fatigue remains difficult to define, and no universally accepted definition has yet been established. It is generally characterised by an overwhelming, persistent, and debilitating sense of exhaustion that impairs functional capacity and limits the performance of everyday activities. Reported prevalence rates of fatigue among patients with musculoskeletal disorders vary considerably, ranging from 35% to 82%. In this review, we examine the impact of fatigue on patients' quality of life, discuss available instruments for its assessment, and consider factors contributing to fatigue, including disease activity and psychological determinants. Furthermore, we summarise experimental studies that have sought to elucidate the biological mechanisms underlying fatigue. The management of fatigue, encompassing both pharmacological and non-pharmacological approaches, is also addressed. Overall, the available evidence concerning fatigue in rheumatic diseases remains limited, and further research is warranted to clarify the contribution of biological mechanisms-such as inflammation, hormonal alterations, and dysfunction of the autonomic nervous system-to the pathogenesis of fatigue.

Pneumocystis jirovecii pneumonia (PJP) is a rare and potentially fatal opportunistic infection in patients with rheumatic diseases with mortality rates exceeding those seen in HIV-infected patients. Although PJP prophylaxis is highly effective, evidence-based guidelines specific to rheumatic disease are lacking resulting in substantial variability in clinical practice. This review examines the existing PJP literature with a focus on efficacy of prophylaxis, adverse effects, and risk factors across rheumatic diseases to inform a pragmatic, risk-stratified approach to prophylaxis. Certain conditions including ANCA-associated vasculitis during induction therapy, anti-MD5+ dermatomyositis and VEXAS syndrome warrant routine prophylaxis in the setting of high-dose glucocorticoid use whereas others conditions, such as Giant Cell Arteritis, do not justify routine prophylaxis. This review provides a practical framework to assist the practicing clinician in making individualized decisions regarding PJP prophylaxis in rheumatic disease.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases with variable extramuscular involvement of the skin, lungs, and other organ systems. Dermatomyositis (DM) is the prototype IIM with skin involvement, but the presence of DM-specific rashes in other IIMs raises questions about whether these conditions are distinct entities, overlapping diseases, or subsets within a DM spectrum. Importantly, distinct cutaneous phenotypes of IIMs may correlate with certain autoantibodies and risk of malignancy or interstitial lung disease. In this review, we outline characteristic DM rashes and describe their prevalence in other IIMs, most notably in antisynthetase syndrome and overlap myositis. We emphasize salient skin findings that may inform diagnosis and prognosis, including some atypical, subtle, or unusual presentations. Finally, we review established and emerging therapies for management of amyopathic or refractory cutaneous DM.