Osteoporosis is a major public health concern, affecting millions globally as well as India leading to a significant morbidity, mortality, and healthcare costs. In India, the prevalence of osteoporosis among Chronic Kidney Disease (CKD) patients on hemodialysis is notably high, with studies showing prevalence of approximately 17 – 31.8%. The burden of osteoporosis in these patients is compounded by CKD-related mineral and bone disorder (CKD-MBD), increasing their risk for fragility fractures and further exacerbating morbidity and healthcare costs. In the general population, osteoporosis typically arises due to age-related bone loss and postmenopausal changes (1, 2). The pathophysiology is more complex and multifactorial, involving CKD-MBD, secondary hyperparathyroidism, altered bone remodeling dynamics, metabolic disturbances and chronic inflammation (3).

CKD is associated with disturbances in calcium, phosphorus, vitamin D, and parathyroid hormone metabolism. These disturbances contribute to abnormalities in bone turnover, mineralization, volume, linear growth, or strength, collectively recognized as CKD-MBD. Patients with CKD are at an increased risk for fractures due to these alterations in bone metabolism, coupled with the direct effects of uremia on bone and muscle function (3, 4). The diagnosis and management of osteoporosis in CKD patients are challenging due to the overlapping features of CKD-MBD and primary osteoporosis, which further complicate the clinical landscape. Traditional diagnostic tools such as dual-energy X-ray absorptiometry (DXA) scans, which measure bone mineral density (BMD), may not fully capture the bone quality in CKD patients. Factors such as vascular calcification and altered bone composition necessitate a re-evaluation of BMD results in this population. Additionally, biomarkers of bone turnover and advanced imaging techniques, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may offer more insight into the underlying bone pathology in CKD patients (5).

Management of osteoporosis in CKD involves a multifaceted approach, including lifestyle modifications, pharmacologic therapies, and addressing the underlying CKD-MBD problem. Pharmacologic options are often limited by the stage of CKD and the overall health status of patients. For example, bisphosphonates, commonly used in the general population, pose risks of adynamic bone and renal toxicity in advanced CKD (6). Newer agents, such as receptor activator of nuclear factor-kB ligand (RANKL) inhibitors, selective estrogen receptor modulators (SERMs), and anabolic medications, such as sclerostin inhibitors, type 1 parathyroid hormone receptor (PTH1R) ligands, offer alternative therapeutic options but require careful consideration in a view of their renal implications and potential side effects (7). Given the complexities involved and the knowledge gap existing among nephrologists regarding management of osteoporosis in the Indian population, a consensus on the optimal approach to diagnose and manage osteoporosis in CKD is essential. Therefore, the objective of this expert consensus was to bridge this gap and provide an overview of current best practices for the diagnosis and management of osteoporosis in CKD. This consensus statement integrates current guidelines, recent research findings, and experts’ opinion to address the unique needs of this patient population, emphasizing the importance of early identification, accurate diagnosis, and individualized treatment strategies. By establishing a standardized approach, we hope to improve patient outcomes, reduce fracture risk, and enhance quality of life for those affected by both osteoporosis and CKD-MBD.

Osteoporosis in chronic kidney disease (CKD) is a complex condition that arises from the intricate interplay between CKD-related mineral and bone disorders (CKD-MBD) and traditional risk factors for osteoporosis. While specific global prevalence rates for CKD-MBD are not uniformly reported, studies indicate that mineral and bone disorders are common among CKD patients, particularly as kidney function declines (9, 10). In the India, CKD-MBD appears to be more prevalent and severe compared to Western populations (11). Few studies conducted in India found a high prevalence of CKD-MBD among CKD patients on hemodialysis, with studies showing that approximately range of 17 - 31.8% of these individuals are affected in India (1, 2). This high prevalence is attributed to factors such as widespread vitamin D deficiency, dietary habits, and limited access to healthcare resources and thereby, linked to the compounded effects of CKD-MBD, which further accelerates bone loss and heightens fracture risk, contributing to significant clinical challenges in managing bone health (1, 2, 11). Moreover, increased CKD-related osteoporosis in developing nations like India is a complex issue with several contributing factors, including limited access to healthcare, economic disparities, nutritional deficiencies, and the prevalence of underlying conditions like diabetes and hypertension. These factors exacerbate the disruption of mineral and bone metabolism that occurs naturally with CKD, leading to weakened bones and increased fracture risk (2). These findings emphasize the importance of early detection and management of CKD-MBD, particularly in regions with higher prevalence rates like India. Additionally, while this consensus statement is primarily informed by Indian experts, it acknowledges that regional differences, such as healthcare infrastructure, disease burden, and access to diagnostic or therapeutic modalities, can influence the implementation of clinical recommendations. The generalizability of these findings to other countries or populations should therefore be considered in the context of local resources and practice environments. This aligns with observations by Kim, 2014 (12) who noted that differences in medical care and social factors between countries can limit the generalizability of global CKD-MBD guidelines. Nevertheless, the core principles align with broader international perspectives and are complementary to regional frameworks like the KDIGO 2017 CKD-MBD guideline updates with Indian commentary (Valson et al., 2020). These efforts reflect a growing need for region-specific adaptations of global guidelines, highlighting the relevance and necessity of such consensus statements tailored to local practice patterns. Patients with CKD are particularly vulnerable to bone loss due to altered calcium and phosphate metabolism, secondary hyperparathyroidism, and vitamin D deficiency. These factors contribute to reduced bone mineral density (BMD) and an increased risk of fractures (3, 4). The diagnosis and management of osteoporosis in CKD require an approach that considers the cross-talk between bone and mineral disorders specific to this population. Managing osteoporosis in CKD is uniquely challenging because standard osteoporosis treatments may not be effective or appropriate in this patient population (13). Therefore, a customized approach that addresses both CKD-related issues and bone health is crucial for improving patient outcomes. The experts in the field reached a consensus on many aspects, including diagnostic challenges and management strategies for patients with osteoporosis in CKD (14). The outcomes of this consensus survey would help to bridge current knowledge gaps and inconsistencies in the current management strategies for osteoporosis in CKD.

Given the high prevalence of this condition and its significant impact on morbidity and mortality, there is an urgent need for evidence-based, expert-driven recommendations. Our expert consensus aimed to address these complexities by developing evidence-based directives and a consensus statement that can guide clinical practice for diagnosing primarily during routine screening and managing the asymptomatic nature of this disease. The recommendations were derived from a systematic evaluation of the literature, coupled with expert opinion, ensuring that the guidelines are both comprehensive and relevant to current clinical challenges. Herein, the expert panel emphasized the need for early and accurate diagnosis, with a multidisciplinary approach to management that includes both pharmacologic and non-pharmacologic interventions (life-style management). By prioritizing the management of renal osteodystrophy (ROD), the recommendations aim to improve patient outcomes through more precise and personalized treatment strategies. The complexity of osteoporosis in CKD requires input from multiple disciplines to ensure that all relevant aspects are addressed (14, 15). By involving experts from nephrology and endocrinology, we were able to incorporate a wide range of perspectives into the discussion and debate.

In expert opinion surveys, consensus is typically achieved when agreement or disagreement falls within the 50 to 80% range (16, 17). However, in our study, the agreement levels ranged from 80 to 100%, reflecting a high degree of alignment among the participating health care professionals. This strong agreement suggests not only a shared understanding of issues involved in managing osteoporosis in CKD patients but also a clear trend toward adopting precise approaches in clinical practice. The expert panel survey began by evaluating the question regarding the most common presentation of CKD-induced osteoporosis, with a focus on whether it is predominantly asymptomatic, detected primarily through screening, and often followed by fragility fractures. This issue is critical because early detection and management hinge on understanding the typical clinical manifestations of osteoporosis in CKD patients. More than 90% of the panelists agreed that asymptomatic presentation is indeed the most common scenario, often identified during routine screening, with bone pain and fragility fractures being less frequent but still significant (18, 19). This consensus highlights the need for proactive screening strategies to identify osteoporosis in its early stages, thereby preventing fractures and improving patient outcomes.

Identifying and managing clinical risk factors for osteoporosis and fracture risk in CKD patients is essential for effective treatment strategies. Several key risk factors have been consistently recognized, including advanced CKD stages with prolonged hemodialysis, a T-score of ≤ −2.5, older age (≥ 65 years), low BMI (≤ 20 kg/m²), postmenopausal status, extended corticosteroid therapy for post-transplant and primary glomerular diseases (>10 mg per day for more than 90 days), hyperparathyroidism, chronic malnutrition, and hyperthyroidism (6, 20, 21). These factors align with recommendations from the European consensus (22), American Society of Nephrology (6), and KDIGO guidelines (18, 19) for managing osteoporosis in CKD patients, underscoring their importance in clinical practice. During the expert panel discussion, a unanimous agreement was reached on these risk factors. However, the panelists emphasized that in addition to patients with a T-score ≤ -2.5, those with normal BMD but a history of fragility fractures should also be considered for osteoporosis treatment. This highlights the importance of a comprehensive approach to patient evaluation, where both bone density metrics and clinical history are critical in guiding management decisions.

Early screening and accurate diagnosis are crucial for implementing effective therapeutic strategies to enhance bone health in this vulnerable population. The diagnosis of osteoporosis traditionally involves evaluating bone quantity through dual energy X-ray absorptiometry (DXA) and vertebral fracture assessment (VFA), and bone quality through trabecular bone score (TBS) assessments. While general population guidelines recommend BMD screening for women ≥65 years and men ≥70 years, in CKD patients, earlier screening is advised, particularly in postmenopausal women and individuals ≥50 years, who are at a higher risk of fractures (23, 24). The panel reached a consensus on the importance of using DXA as the primary tool for osteoporosis screening in CKD patients. Furthermore, the use of fracture risk assessment tool (FRAX) for fracture risk assessment in CKD patients was discussed, noting its limitations as CKD and GFR levels are not included in the FRAX calculation. Despite this, the panel supported its use, referencing findings of Whitlock and co-workers (25), who demonstrated a stronger relationship between FRAX scores and fracture risk in CKD patients compared to those with preserved eGFR. Importantly, the World Health Organization (WHO) has clarified that the FRAX^® tool is not a WHO-developed or endorsed tool. WHO has no involvement in the development, validation, or evaluation of FRAX^® algorithms, data, or embedded treatment recommendations (26). Additionally, the panel suggested that, wherever available, combining BSAP and iPTH could be more reliable than individual measurement for distinguishing between high and low bone turnover diseases, further enhancing the precision of osteoporosis management in CKD.

The management of osteoporosis in patients with CKD, necessitating a multidisciplinary approach that incorporates both non-pharmacological life style modifications and pharmacological strategies. The selection of treatment should be tailored to the individual fracture risk, taking into account the continuum from low to very high risk. Evaluating bone turnover status is critical, as it informs the choice of therapy, ensuring that it aligns with the patient’s bone metabolism, whether it is high, low, or adynamic. For instance, in advanced CKD, or in hemodialysis patients with eGFR < 40 ml/min, bisphosphonates must be used cautiously due to the risks of adynamic bone. While randomized controlled trials (RCTs) have not shown any significant decline in eGFR with the use of oral bisphosphonates, intravenous (IV) bisphosphonates are associated with an increased risk of acute kidney injury (AKI). Therefore, IV bisphosphonates require particular caution in this patient population (13). Teriparatide, while effective, should be administered carefully in severe renal impairment due to delayed elimination and reduced efficacy in the presence of elevated PTH levels (27). Denosumab, a RANKL inhibitor, has shown to significantly increase bone mineral density and reduce fracture risk after six months of therapy, without the nephrotoxic concerns seen with other options (13, 28). In post hoc analysis of FREEDOM trial and its extension (29), mild-to-moderate CKD patients were evaluated for long-term safety and efficacy of denosumab. Participants across all CKD subgroups showed consistent BMD gains, low fracture rates, and comparable adverse event profiles. Safety and efficacy of denosumab remained stable in patients with CKD stages 2 and 3 over the study period. However, regular monitoring of serum calcium and PTH levels is essential to ensure safety, especially in patients with advanced CKD particularly hemodialysis patients, where the risk of hypocalcemia is higher especially if patients had not received prior vitamin D and calcium supplements (6, 13, 28). With appropriate monitoring, it remains a viable option for managing CKD-associated osteoporosis. In a line with this, the expert panel emphasized the necessity of a multidisciplinary approach in managing CKD-induced osteoporosis, however they also suggested that renal osteodystrophy (ROD) management is a prerequisite before addressing osteoporosis (6, 13). The treatment regimen should start with lifestyle modifications and ROD management, followed by specific therapies based on bone turnover status, and serum BSAP levels (13). For patients with high bone turnover, bisphosphonates or denosumab are recommended for those with eGFR >40 mL/min/1.73m², while denosumab alone is suggested for those patient with eGFR <40 ml/min (6, 13). Conversely, anabolic agents are preferred for low turnover bone (6). This approach ensures that treatments are not only effective but also safe, minimizing the risk of further complications in this high-risk population. In determining the appropriate treatment approach, the choice between anti-resorptive or anabolic therapy should consider estimated fracture risk, side effect profile, local availability, and cost. Table 3 provides detailed information on anabolic and anti-resorptive therapies, including their mechanisms of action and potential side effects.

Frequent monitoring is a critical aspect of managing osteoporosis in CKD patients, as it ensures that the chosen treatment strategies are both effective and safe over time. The importance of regular follow-up is well-documented/reported in numerous guidelines and recommendations, emphasizing the need for ongoing assessment to adapt therapies as needed (16, 18, 22, 23). Our expert panel concurs with these guidelines and recommendations, advocating for consistent follow-up in CKD patients with osteoporosis. At each follow-up visit, they also suggested that it is essential to monitor changes in bone mineral density (BMD) using DXA scans, as this provides a reliable measure of treatment efficacy and helps guide adjustments in therapy. DXA scans are particularly valuable in this context, offering a precise and non-invasive method to track bone density changes over time. By integrating regular DXA assessments (1–2 yearly) into the follow-up routine, clinicians can better manage osteoporosis in CKD patients, ensuring that the therapeutic approach remains aligned with the patient’s evolving needs. This approach not only optimizes bone health but also mitigates the risk of fractures, a significant concern in this vulnerable population (6, 13, 23). The panel’s recommendation aligns with the broader consensus that regular (16, 22), comprehensive monitoring is vital for effective osteoporosis management in CKD patients.

Formulating an algorithm for the diagnosis and management of osteoporosis in CKD is a promising step towards standardizing care, but it requires careful consideration and thorough analysis. In a line with this, expert panel proposed the comprehensive algorithmic flow chart that would be helpful for managing osteoporosis in CKD patients, which aligns with the algorithm of Egyptian recommendations suggest by El Miedany and co-workers (2). While patient representatives were not included in this consensus, we acknowledge their importance and plan to include their perspectives in future updates to enhance relevance and applicability.

One of the limitation of this study is its reliance on expert opinion, which, while valuable, may introduce bias and does not replace the need for robust clinical trial data. Additionally, the lack of a Delphi method with multiple rounds of feedback could have limited the depth of consensus, potentially overlooking different opinions that may have emerged with further discussions. Further, our consensus recommendations were tailored to the Indian healthcare context, therefore we acknowledge that variations in healthcare infrastructure, resource availability, and patient demographics across different regions may affect their applicability.

This study provides a comprehensive expert consensus on the diagnosis and management of osteoporosis in patients with CKD. The recommendations emphasize the importance of a multidisciplinary approach, early screening, and tailored treatment strategies that consider both bone health and the underlying CKD. While further research and larger-scale studies are needed, these consensus recommendations offer a practical framework for clinicians managing osteoporosis in CKD, aiming to improve patient outcomes and address the challenges posed by this complex condition.