Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

Orthopedic Surgical Treatment of Patients with Tumor-induced Osteomalacia Located in the Hip Bones: A Retrospective Analysis of 10 Years in a Single Center.

OBJECTIVE: The orthopedic surgical treatment strategies for patients with tumor-induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in-depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor-induced osteomalacia (TIO), whose causative tumors are located in the hip bones. METHODS: A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub-professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery-related data, perioperative changes in blood phosphorus levels, and postoperative follow-up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non-normally distributed data are shown as the means and 25th and 75th interquartile ranges. RESULTS: The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. CONCLUSION: In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis.

The role of GDF5 in regulating enthesopathy development in the Hyp mouse model of XLH.

X-linked hypophosphatemia (XLH) is caused by mutations in PHEX, leading to rickets and osteomalacia. Adults affected with XLH develop a mineralization of the bone-tendon attachment site (enthesis), called enthesopathy, which causes significant pain and impaired movement. Entheses in mice with XLH (Hyp) have enhanced Bone Morphogenetic Protein (BMP) and Indian hedgehog (IHH) signaling. Treatment of Hyp mice with the BMP signaling blocker palovarotene attenuated BMP/IHH signaling in Hyp entheses, thus indicating that BMP signaling plays a pathogenic role in enthesopathy development and that IHH signaling is activated by BMP signaling in entheses. It was previously shown that mRNA expression of Gdf5 is enhanced in Hyp entheses at P14. Thus, to determine a role for GDF5 in enthesopathy development, Gdf5 was deleted globally in Hyp mice and conditionally in Scx + cells of Hyp mice. In both murine models, BMP/IHH signaling was similarly decreased in Hyp entheses, leading to decreased enthesopathy. BMP/IHH signaling remained unaffected in WT entheses with decreased Gdf5 expression. Moreover, deletion of Gdf5 in Hyp entheses starting at P30, after enthesopathy has developed, partially reversed enthesopathy. Taken together, these results demonstrate that while GDF5 is not essential for modulating BMP/IHH signaling in WT entheses, inappropriate GDF5 activity in Scx + cells contributes to XLH enthesopathy development. As such, inhibition of GDF5 signaling may be beneficial for the treatment of XLH enthesopathy.

X-linked hypophosphatemia (XLH) is a rare bone disorder that leads to short stature and poorly mineralized bones. As adults, patients with XLH often develop a mineralization of the bone-tendon attachment site, called enthesopathy, that results in significant pain. We previously showed that Achilles bone-tendon attachment sites (entheses) in mice with XLH (Hyp) have an enthesopathy characterized by increased Bone Morphogenetic Protein (BMP) signaling. In the current studies, we show that treating Hyp mice with the BMP signaling inhibitor palovarotene prevents enthesopathy, demonstrating that the increased BMP signaling in Hyp entheses leads to enthesopathy development. We also reported that expression of Gdf5, which activates BMP signaling, is enhanced in Hyp entheses. Therefore, to determine if the enhanced Gdf5 expression leads to the increased BMP signaling seen Hyp entheses, Gdf5 was deleted from Hyp mice and also deleted specifically in the entheses of Hyp mice. In both mouse models, enthesopathy development was attenuated, demonstrating that the increased Gdf5 expression in Hyp entheses plays a role in enthesopathy development. These data indicate that blocking GDF5 and BMP signaling may prevent enthesopathy in patients with XLH.

Challenges in the diagnosis and management of tumor-induced osteomalacia: A case report.

The present case report is aimed to highlight the difficulty and the reason for the delayed diagnosis of phosphaturic mesenchymal tumors, emphasizing the need of standardized protocols for diagnosis, surgery and follow-up in high-volume hospitals. The clinical signs and symptoms, diagnostic and therapeutic procedures, immunohistological features were analyzed. Delayed diagnosis of phosphaturic mesenchymal tumor was primarily due to non-specific clinical symptoms such as fatigue, muscular and bone pain, and multiple fractures. This cryptic clinical picture made the diagnosis tricky that led to treatment of patient for non-specific pain and stress fractures before to consider the tumor-induced osteomalacia syndrome. Some well-documented studies were found in the literature in which the history of trauma is a critical trigger of glomus tumors. Extra-subungual tumors most frequently occur in the knee and ankle regions, particularly among young adults, and the diagnosis is typically made approximately 7.2 years after initial symptom onset. The difficult tumor localization represented an additional obstacle to the prompt treatment, leading to delayed curative surgery.

Correction to: "Emerging Role of Gallium-68 DOTANOC PET/CT Guided Radiofrequency Ablation in the Treatment of Tumor-induced Osteomalacia".

[This corrects the article DOI: 10.1210/jcemcr/luae044.].

Exploring the Interplay between Vitamin D, Insulin Resistance, Obesity and Skeletal Health.

Vitamin D (ViD), plays an important role in calcium absorption and bone mineralization, is associated with bone mineral density. Severe deficiency in ViD has long been linked to conditions such as rickets in children and osteomalacia in adults, revealing its substantial role in skeletal health. Additionally, investigations show an existing interconnection between ViD and insulin resistance (Ins-R), especially in patients with type 2 diabetes mellitus (T2DM). Obesity, in conjunction with Ins-R, may augment the risk of osteoporosis and deterioration of skeletal health. This review aims to examine recent studies on the interplay between ViD, Ins-R, obesity, and their impact on skeletal health, to offer insights into potential therapeutic strategies. Cochrane Library, Google Scholar, and Pubmed were searched to investigate relevant studies until December 2023. Current research demonstrates ViD's impact on pancreatic ß-cell function, systemic inflammation, and insulin action regulation. Our findings highlight an intricate association between ViD, Ins-R, obesity, and skeletal health, providing a perspective for the prevention and/or treatment of skeletal disorders in patients with obesity, Ins-R, and T2DM.

Optimisation of vitamin D status in global populations.

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.

Long-Term Follow-Up Data of Tumor-Induced Osteomalacia Managed with Surgery and/or Radiofrequency Ablation from a Single Center.

Data on radiofrequency ablation (RFA) in tumor-induced osteomalacia (TIO) are restricted to case reports (~ 11 patients) and long-term follow-up data are further scarce. We describe our experience on managing TIO from a tertiary care center in India. Retrospective study of patients with localized TIO was performed and clinical, biochemical, treatment and follow-up details were retrieved. Normalization of serum phosphorus in absence of phosphate supplementation was defined as remission. Of 33 patients (23 males), 24 patients underwent surgery as first-line treatment, and early remission, delayed remission (> 1 month for phosphorus normalization) and persistence were observed 12, 3, and 9 patients at a median follow-up of 5 (4-9) years. The gender, age, tumor size, location of tumors and FGF23 levels were not statistically different in patients who were in remission after surgery versus those with persistent disease. Second/third line treatment included conventional medical treatment and/or repeat surgery (n = 3), radiotherapy (n = 3), peptide receptor radionuclide therapy (n = 1), RFA (n = 1). Two patients had transient worsening (weeks) of weakness post-surgery. 10 patients underwent RFA (first-line n = 9); at the last follow-up 5 (4-10) years, 7 are in remission. Two of three persistent disease patients had large tumors (5.6 and 3.6 cm). There were no RFA-related complications except local ulcer in one. Although persistent disease was present in a few patients in both arms, there was no recurrence in either RFA or surgical cohort. RFA provide durable response similar to surgery, persistence requires multi-modality treatment.

18F-AlF-NOTA-octreotide PET/CT in the localization of tumor-induced osteomalacia: case series and literature review.

Introduction: This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT). Methods: We analyzed TIO patients who underwent 18F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed. Results: 6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent 18F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm3). Conclusion: The implementation of whole-body 18F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of 18F-OC PET/CT in managing TIO.

Displaced Proximal Tibia Fracture After Proximal Tibial Autograft Harvest: A Case Report.

Background: A 60-year-old female underwent proximal tibial autograft harvest for a Cotton osteotomy. Her postoperative course was complicated by psychogenic non-epileptic seizure (PNES) episodes leading to unintentional weightbearing. Knee radiographs at 6 weeks post-procedure demonstrated a displaced proximal tibia fracture through the autograft harvest site. Further clinical review revealed metabolic derangements consistent with secondary hyperparathyroidism. Initial nonoperative treatment led to atrophic varus nonunion requiring definitive treatment with total knee arthroplasty with revision components. Conclusion: This case describes a rare complication of proximal tibial autograft harvest and highlights the importance of preoperative metabolic workup and bone health optimization.Level of Evidence: IV.

Healthcare resource use associated with tumor-induced osteomalacia: a literature review.

CONTEXT: Tumor-induced osteomalacia (TIO) is an ultra-rare, paraneoplastic syndrome caused by tumors that secrete fibroblast growth factor 23 (FGF23). Initial signs and musculoskeletal symptoms can be non-specific and unrecognized, leading to long delays in diagnosis and treatment, which results in severe and progressive disability in patients with TIO. This review aimed to identify published evidence on healthcare resource use in TIO to better understand the burden of the disease. EVIDENCE ACQUISITION: A targeted literature review was conducted to identify publications reporting on disease characteristics and healthcare resource use associated with TIO. EVIDENCE SYNTHESIS: In total, 414 publications were included in the review, of which 376 were case reports. From the case reports, data on 621 patients were extracted. These patients had a mean (standard deviation) age of 46.3 (15.8) years; 57.6% were male. Mean time from first symptoms to diagnosis of TIO was 4.6 (4.7) years and, in cases where imaging tests were reported, patients underwent a mean of 4.1 (2.7) procedures. Tumor resection was attempted in 81.0% of patients and successful in 67.0%. Fracture was reported in 49.3% of patients. Results from association analyses demonstrated that longer time to diagnosis was associated with poorer tumor resection outcomes and a higher probability of tumor recurrence. Unfavorable tumor resection outcomes were associated with greater use of pharmacologic treatment and a greater likelihood of orthopedic surgery. CONCLUSION: TIO is associated with a substantial healthcare resource burden. Improvements in the diagnostic process could lead to better management of TIO, thereby benefiting patients and reducing that burden.

Skeletal fluorosis: an uncommon cause, yet a rescue treatment?

PURPOSE: Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases. CASE PRESENTATION: A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden. CONCLUSION: Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels.

A Rare Association Between Osteomalacia, Phosphaturic Mesenchymal Tumor, and Ovarian Cancer: A Case Report and Literature Review.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia, bone mineralization disorders with increased risk of fragility fractures, muscle pain, and progressive weakness. TIO has been associated with increased production of the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) usually by mesenchymal tumors of soft tissue or bone (Phosphaturic Mesenchymal Tumors-PMTs). In rare cases TIO may be observed in association with other malignancies. We report the case of a 66-year-old woman with an occasional diagnosis of both a PMT and an ovarian cancer during the evaluation of TIO. We also systematically review the literature to discover possible correlations between osteomalacia, FGF23 production, and ovarian cancer. Four studies were eligible for the analysis. Two case reports described an association between TIO development and ovarian cancer, whereas the two case-control studies hypothesized a possible correlation between FGF/FGF receptor axis and cancer development. Although it does not provide conclusive evidence regarding the association between TIO and ovarian cancer, this case report highlights the possibility that in the diagnostic workup of suspected TIO, both FGF23-secreting tumors distinct from PMT and tumors unrelated to the clinical presentation of TIO could be identified. This information is important for guiding successful tumor staging and determining the necessity for surgical intervention and/or eventual adjuvant therapy.

Chronic bromine intoxication complicated with Fanconi syndrome: A case report.

In this report, we describe a unique case of an 80-year-old woman who developed chronic bromine poisoning due to the prolonged ingestion of over-the-counter (OTC) medication containing bromovalerylurea (BVU), thus leading to the onset of drug-induced partial Fanconi syndrome and resultant osteomalacia. The patient's condition improved following the cessation of bromide intake. This case highlights the potential risks of chronic BVU exposure and the importance of caution regarding the use of OTC medications containing BVU.

Tumor-induced osteomalacia: A systematic literature review.

Introduction: Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor. Material and methods: We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online. Results: We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively. Conclusion: TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.

Unusual presentation of tumor-induced osteomalacia mismanaged due to misdiagnosis: A literature review based on a case report.

Key Clinical Message: Tumor-induced osteomalacia is a rare but potentially serious disease with nonspecific misguiding manifestations that can result in a wrong diagnosis and being treated for rheumatologic or other similar diseases. In patients with unexpected fractures, resistant musculoskeletal pains, and hypophosphatemia, this diagnosis should be considered by the physicians and approached through a complete history taking, physical exam laboratory, and radiologic evaluation to give the opportunity of on-time treatment to the patient. Abstract: Tumor-induced osteomalacia (TIO) is an uncommon mesenchymal tumor that results in disproportionate phosphorus excretion, primarily leading to bone-related symptoms. Laboratory, imaging, and histopathological evaluation can confirm this pathologic condition. In this case, we present the history and subsequent clinical parts of a 50-year-old woman who presented with an unusual presentation of generalized musculoskeletal pains and a right ankle mass. Her disease was diagnosed with multidisciplinary evaluation and was approached by a surgical treatment. The patient was treated with total resection of the tumor, which led to complete resolution of musculoskeletal and metabolic abnormalities, which were resolved following total tumor resection. TIO is a paraneoplastic disease that results in abnormal secretion of phosphatonins, particularly fibroblast growth factor 23 (FGF23). This can cause hypophosphatemia, hyperparathyroidism, lower bone density, and increased risk of pathologic fractures. These tumors are mostly cured by surgical ± radiotherapy. The present study aims to provide insight into the fact that a TIO diagnosis is not always straightforward. However, in suspicious cases such as unexplained hypophosphatemia, it should be considered to prevent delayed diagnosis of the progressive pathology. The earlier treatment can prevent several complications and reduce the risk of mortality.

Major Pancreatic Resection Increases Bone Mineral Density Loss, Osteoporosis, and Fractures.

OBJECTIVE: To assess whether long-term survivors of pancreatic surgery show increased risk to develop impaired bone mineral density, osteoporosis, and vitamin D deficiency. BACKGROUND: Pancreatic resection poses a risk for malabsorption of fat-soluble vitamins and other micronutrients essential for bone mineralization. Here, we evaluated the long-term effects of pancreatic resection on bone mineral density (BMD) and its clinical sequelae. METHODS: This was a two-pronged analysis of post-pancreatectomy patients with a follow-up period greater than 3 years comprising (1) a large, propensity score-matched, cohort study based on a multinational federated research network (FRN) and (2) a retrospective single institution review of clinical and radiographic patient data. In the FRN analysis, an initial cohort of 8,423 post-pancreatectomy patients were identified and propensity score-matched with normal controls. The primary endpoint was the 10-year risk of developing osteoporotic pathological fractures and secondary endpoints included diagnosis of osteoporosis, vitamin-D deficiency, and related therapies. The single institution retrospective analysis identified 224 patients who underwent pancreatic resection between 2005 and 2019. BMD was quantified in CT images acquired before and after surgery. BMD trends and related factors were assessed in a time-series mixed effect linear regression model. RESULTS: A total of 8,080 propensity score-matched pairs were included in the FRN analysis. The analysis revealed a 2.4-fold increase in pathological fractures (P<0.0001) and 1.4-1.5 fold increase in osteoporosis/osteomalacia (P<0.0001) and vitamin-D deficiency (P<0.0001) in post-pancreatectomy patients. Vitamin-D supplements were more common in the pancreatectomy group (OR 1.4, 95% CI 1.28-1.53, P<0.0001), as were specific osteoporosis/osteomalacia treatments such as calcitonin, denosumab, romosozumab, abaloparatide, and teriparatide (OR 2.24, 95%CI 1.69-2.95, P<0.0001). Retrospective analysis of CT imaging revealed that BMD declined more rapidly following pancreatic resection compared to normal historical controls (P=0.015). Older age, pancreatic cancer, and pancreaticoduodenectomy were associated with increased rates of BMD loss (P<0.05, each). CONCLUSIONS: After pancreatic resection, patients are at higher risk for BMD loss and subsequent fractures. As the cohort of pancreatic resection survivorship grows, attention will need to be paid to focused prevention efforts to reduce BMD loss, osteoporosis, and fractures in these vulnerable patients, with specific attention to the pancreatic cancer population.