Influence of Hyponatremia on Spinal Bone Quality and Fractures Due to Low-Energy Trauma

Background and Objectives: Hyponatremia is the most common electrolyte disorder in elderly and associated with increased risk of falls. Clinical studies as well as small animal experiments suggested an association between chronic hyponatremia and osteoporosis. Furthermore, it has been assumed that subtle hyponatremia may be an independent fracture risk in the elderly. Therefore, this study was designed to evaluate the possible influence of chronic hyponatremia on osteoporosis and low-energy fractures of the spine. Materials and Methods: 144 patients with a vertebral body fracture (mean age: 69.15 ± 16.08; 73 females and 71 males) due to low-energy trauma were treated in a level one trauma center within one year and were included in the study. Chronic hyponatremia was defined as serum sodium < 135 mmol/L at admission. Bone mineral density (BMD) of the spine was measured using quantitative computed tomography in each patient. Results: Overall, 19.44% (n = 28) of patients in the low-energy trauma group had hyponatremia. In the group with fractures caused by low-energy trauma, the proportion of hyponatremia of patients older than 65 years was significantly increased as compared to younger patients (p** = 0.0016). Furthermore, there was no significant gender difference in the hyponatremia group. Of 28 patients with chronic hyponatremia, all patients had decreased bone quality. Four patients showed osteopenia and the other 24 patients even showed osteoporosis. In the low-energy trauma group, the BMD correlated significantly with serum sodium (r = 0.396; p*** < 0.001). Conclusions: The results suggest that chronic hyponatremia affects bone quality. Patients with chronic hyponatremia have an increased prevalence of fractures after low-energy trauma due to a decreased bone quality. Therefore, physicians from different specialties should focus on the treatment of chronic hyponatremia to reduce the fracture rate after low-energy trauma, particularly with elderly patients.

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MECHANISMS IN ENDOCRINOLOGY: Endogenous subclinical hypercortisolism and bone: a clinical review

Acta Endocrinologica ◽

10.1530/eje-16-0289 ◽

2016 ◽

Vol 175 (6) ◽

pp. R265-R282 ◽

Cited By ~ 25

Author(s):

I Chiodini ◽

C Eller Vainicher ◽

V Morelli ◽

S Palmieri ◽

E Cairoli ◽

...

Keyword(s):

Bone Quality ◽

Fragility Fractures ◽

Primary Osteoporosis ◽

Mineral Density ◽

Subclinical Hypercortisolism ◽

Biochemical Tests ◽

Glucocorticoid Sensitivity ◽

Increased Risk ◽

The Individual ◽

Specific Symptoms

In recent years, the condition of subclinical hypercortisolism (SH) has become a topic of growing interest. This is due to the fact that SH prevalence is not negligible (0.8–2% in the general population) and that, although asymptomatic, this subtle cortisol excess is not harmless, being associated with an increased risk of complications, in particular of osteoporosis and fragility fractures. As specific symptoms of hypercortisolism are absent in SH, the SH diagnosis relies only on biochemical tests and it is a challenge for physicians. As a consequence, even the indications for the evaluation of bone involvement in SH patients are debatable and guidelines are not available. Finally, the relative importance of bone density, bone quality and glucocorticoid sensitivity in SH is a recent field of research. On the other hand, SH prevalence seems to be increased in osteoporotic patients, in whom a vertebral fracture may be the presenting symptom of an otherwise asymptomatic cortisol excess. Therefore, the issue of who and how to screen for SH among the osteoporotic patients is widely debated. The present review will summarize the available data regarding the bone turnover, bone mineral density, bone quality and risk of fracture in patients with endogenous SH. In addition, the role of the individual glucocorticoid sensitivity in SH-related bone damage and the problem of diagnosing and managing the bone consequences of SH will be reviewed. Finally, the issue of suspecting and screening for SH patients with apparent primary osteoporosis will be addressed.

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Biologicals and bone loss

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x12441275 ◽

2012 ◽

Vol 4 (4) ◽

pp. 245-247 ◽

Cited By ~ 3

Author(s):

Charlotte L.M. Krieckaert ◽

Willem F. Lems

Keyword(s):

Bone Loss ◽

Active Rheumatoid Arthritis ◽

Osteoporotic Fractures ◽

Fracture Rate ◽

Healthy Controls ◽

Mineral Density ◽

Common Pathway ◽

Inflammatory Joint Diseases ◽

Nonvertebral Fractures ◽

Increased Risk

Inflammatory joint diseases are associated with extra-articular side effects including bone involvement.There is an increased risk of osteoporotic fractures. The pathogeneses of local and generalized bone loss share a common pathway. Early and active rheumatoid arthritis is associated with longitudinal observed bone loss and fracture rate is of vertebral and nonvertebral fractures is doubled compared with matched healthy controls. Lowering disease activity with TNF inhibitors or is associated with stabilisation of bone mineral density by counteracting elevated bone resorption.

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SAT0468 EFFECTS OF ANDROGEN DEPRIVATION THERAPY ON BONE QUALITY (TBS) IN PATIENTS WITH PROSTATE CANCER

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2644 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1191.2-1192

Author(s):

S. Garcia-Cirera ◽

E. Casado ◽

J. Muñoz ◽

L. Del Río ◽

M. Arévalo ◽

...

Keyword(s):

Prostate Cancer ◽

Lumbar Spine ◽

Androgen Deprivation Therapy ◽

Bone Quality ◽

Bone Microarchitecture ◽

Androgen Deprivation ◽

Mineral Density ◽

Increased Risk ◽

One Year

Background:Androgen deprivation therapy (ADT), by inducing severe hypogonadism, leads to a loss of bone mineral density (BMD) and an increased risk of fragility fractures after 6 months of treatment in men with prostate cancer1. However, its effect on bone quality has not been described.Objectives:To evaluate the changes on bone microarchitecture (bone quality) assessed by TBS (trabecular Bone Score) in male patients with prostate cancer after one year of treatment with ADT.Methods:All patients diagnosed with prostate cancer candidates for long-term ADT admitted to Urology department of Hospital Universitari Parc Tauli (reference population of 450,000 inhabitants) between April 2017 and December 2019 were included. Patients who received chemotherapy, previous hormonal therapy or specific treatment for osteoporosis in the last year or those who had a very impaired functional capacity (Barthel index <30) were excluded.Demographic, clinical and analytical data (testosterone, calcium, phosphorous, alkaline phosphatase, 25-hidroxyvitamin D, PTH) were collected in all patients. A bone densitometry (GE-Lunar Prodigy) including the measurement of lumbar spine TBS (L1-L4) using Medimaps Software was performed at baseline and at 12 months of treatment with ADT.Results:78 patients were included. Mean age 77,9±8,3 years. The median Gleason score was 7,88±1,05. 3 patients had previous fragility fracture (one sacral fracture, one fibula and one multiple vertebral fracture). Baseline analytical values in patients were the following: testosterone11,6±74,9 nmol/L.; 25-hidroxyvitamin D 20,8±10,4 ng/ml; PTH 51,8±23,0 pg/ml; CTX 0,58±0,66. The daily calcium intake was 573±207 mg/day.According to BMD, 17 patients (21,8%) had osteoporosis before starting ADT, with the following average T-score values: lumbar spine +0,15±1,85, femoral neck -1,75±1,00, and total hip -1,19±1,16. Mean baseline TBS value of the entire cohort was 1,279±0,122. 30,5% of the patients showed very degraded microarchitecture (TBS<1,230), 28,8% had partially degraded microarchitecture (TBS 1,230-1,310) and in 40,7% showed normal microarchitecture (TBS >1,310).After one year of ADT treatment, TBS mildly worsened in this cohort, with a median value of 1,256±0,131 (p = NS). However up to 43% of patients reached highly degraded microarchitecture, 27% partially degraded and only 29,5% had a normal TBS (p = NS).Conclusion:Most patients with prostate cancer have an altered bone quality before starting ADT. After 12 months of treatment, the percentage of patients with highly degraded bone microarchitecture increases, although not significantly. More studies are needed to confirm this trend and to evaluate if these patients present more long-term fractures.References:[1]Lee R, et al. Bone 2011; 48 (1): 88-95Disclosure of Interests:Silvia Garcia-Cirera: None declared, Enrique Casado Speakers bureau: UCB, Lilly, Amgen, Theramex, Gebro, Gedeon-Richter, Stada, Jesús Muñoz: None declared, Luis Del Río: None declared, Marta Arévalo: None declared, Menna Rusiñol: None declared, Noemí Navarro: None declared, Víctor Parejo: None declared, Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly

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Changes in Cortical Volumetric Bone Mineral Density and Thickness, and Trabecular Thickness in Lactating Women Postpartum

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-2825 ◽

2015 ◽

Vol 100 (2) ◽

pp. 535-543 ◽

Cited By ~ 22

Author(s):

P. Brembeck ◽

M. Lorentzon ◽

C. Ohlsson ◽

A. Winkvist ◽

H. Augustin

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Geometric Mean ◽

Quantitative Computed Tomography ◽

Volumetric Bone Mineral Density ◽

Postpartum Women ◽

Mineral Density ◽

Trabecular Thickness ◽

Increased Risk ◽

Dimensional Parameters

Abstract Context: Lactation is associated with decreased areal bone mineral density (aBMD). Replenishment occurs especially after ceased lactation. Changes in volumetric bone mineral density (vBMD), microstructure, and dimensional parameters are unknown and may clarify the role of lactation for skeletal health. Objective and Main Outcomes: The objective of the study was to test the hypothesis that lactation is associated with changes in aBMD, vBMD, microstructure, and dimensional parameters. Design: At baseline (0.5 mo after delivery) and 4, 12, and 18 months thereafter, bone was assessed using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Participants and Setting: Eighty-one fair-skinned postpartum women and 21 controls aged 25–40 years were recruited. The completion ratio was 73%. Postpartum women were categorized depending on duration of lactation: 0–3.9, 4–8.9, and 9 months or longer. Results: During the first 4 months, aBMD decreased at several sites (geometric mean ± SE; −0.73% ± 0.21% to −3.98% ± 0.76%) in women lactating at least 4 months. During the same time, cortical vBMD at the ultradistal tibia decreased in women lactating 4–8.9 months (−0.26% ± 0.08%) and 9 months or longer (−0.49% ± 0.10%). At 12 months postpartum, cortical thickness (≥9 mo, −2.48% ± 0.41%) and trabecular thickness (4–8.9 mo, −2.14% ± 0.92%; ≥ 9 mo, −2.56% ± 1.21%) also were lower than baseline. No decreases were found in women lactating less than 4 months or in controls in these parameters. At 18 months postpartum, both cortical vBMD (≥9 mo, −0.77% ± 0.17%) and trabecular thickness (4–8.9 mo, −2.25% ± 1.25%; ≥ 9 mo, −3.21% ± 1.41%) were lower in women with long lactation. Conclusions: Decreases in cortical vBMD, thickness, and trabecular thickness at the ultradistal tibia were found in women lactating 4 months or longer. Longer follow-up is needed to confirm whether women with extended lactation recover fully or whether the changes could potentially lead to an increased risk of fracture in later life.

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Differential Effects of PPAR-γ Activation versus Chemical or Genetic Reduction of DPP-4 Activity on Bone Quality in Mice

Endocrinology ◽

10.1210/en.2010-1098 ◽

2010 ◽

Vol 152 (2) ◽

pp. 457-467 ◽

Cited By ~ 51

Author(s):

Kimberly A. Kyle ◽

Thomas L. Willett ◽

Laurie L. Baggio ◽

Daniel J. Drucker ◽

Marc D. Grynpas

Keyword(s):

Bone Mineral Density ◽

Bone Quality ◽

Bone Mineral ◽

Volumetric Bone Mineral Density ◽

Trabecular Architecture ◽

Bone Mechanics ◽

Wild Type ◽

Mineral Density ◽

Female Mice ◽

Increased Risk

Abstract Patients with type 2 diabetes mellitus have an increased risk of fracture that can be further exacerbated by thiazolidinediones. A new class of antidiabetic agents control glucose through reduction of dipeptidyl peptidase-4 (DPP-4) activity; however the importance of DPP-4 for the control of bone quality has not been extensively characterized. We compared the effects of the thiazolidinedione pioglitazone and the DPP-4 inhibitor sitagliptin on bone quality in high-fat diet (HFD)-fed wild-type mice. In complementary studies, we examined bone quality in Dpp4+/+ vs. Dpp4−/− mice. Pioglitazone produced yellow bones with greater bone marrow adiposity and significantly reduced vertebral bone mechanics in male, female, and ovariectomized (OVX) HFD fed female mice. Pioglitazone negatively affected vertebral volumetric bone mineral density, trabecular architecture, and mineral apposition rate in male mice. Sitagliptin treatment of HFD-fed wild-type mice significantly improved vertebral volumetric bone mineral density and trabecular architecture in female mice, but these improvements were lost in females after OVX. Genetic inactivation of Dpp4 did not produce a major bone phenotype in male and female Dpp4−/− mice; however, OVX Dpp4−/− mice exhibited significantly reduced femoral size and mechanics. These findings delineate the skeletal consequences of pharmacological and genetic reduction of DPP-4 activity and reveal significant differences in the effects of pioglitazone vs. sitagliptin vs. genetic Dpp4 inactivation on bone mechanics in mice.

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Local bone quality measure and construct failure prediction: a biomechanical study on distal femur fractures

Archives of Orthopaedic and Trauma Surgery ◽

10.1007/s00402-021-03782-7 ◽

2021 ◽

Author(s):

Dominic Gehweiler ◽

Ursula Styger ◽

Boyko Gueorguiev ◽

Christian Colcuc ◽

Thomas Vordemvenne ◽

...

Keyword(s):

Bone Strength ◽

Bone Quality ◽

Distal Femur ◽

Quantitative Computed Tomography ◽

Biomechanical Testing ◽

Peak Torque ◽

Biomechanical Study ◽

Mineral Density ◽

Femur Fractures ◽

Local Bone

Abstract Introduction The aim of this investigation was to better understand the differences in local bone quality at the distal femur and their correlation with biomechanical construct failure, with the intention to identify regions of importance to optimize implant anchorage. Materials and methods Seven fresh–frozen female femurs underwent high-resolution peripheral quantitative computed tomography (HR-pQCT) to determine bone mineral density (BMD) within three different regions of interest (distal, intermedium, and proximal) at the distal femur. In addition, local bone quality was assessed by measuring the peak torque necessary to break out the trabecular bone along each separate hole of a locking compression plate (LCP) during its instrumentation. Finally, biomechanical testing was performed using cyclic axial loading until failure in an AO/OTA 33 A3 fracture model. Results Local BMD was highest in the distal region. This was confirmed by the measurement of local bone quality using DensiProbe™. The most distal holes represented locations with the highest breakaway torque resistance, with the holes on the posterior side of the plate indicating higher values than those on its anterior side. We demonstrated strong correlation between the cycles to failure and local bone strength (measured with DensiProbe™) in the most distal posterior screw hole, having the highest peak torque. Conclusion The local bone quality at the distal femur indicates that in plated distal femur fractures the distal posterior screw holes seem to be the key ones and should be occupied. Measurement of the local bone strength with DensiProbe™ is one possibility to determine the risk of construct failure, therefore, thresholds need to be defined.

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Bone Quality in CKD Patients: Current Concepts and Future Directions – Part I

Kidney Diseases ◽

10.1159/000515534 ◽

2021 ◽

pp. 1-10

Author(s):

Kamyar Asadipooya ◽

Mohamed Abdalbary ◽

Yahya Ahmad ◽

Elijah Kakani ◽

Marie-Claude Monier-Faugere ◽

...

Keyword(s):

Fracture Risk ◽

Bone Quality ◽

Bone Health ◽

New Technologies ◽

Trabecular Bone Score ◽

Qualitative Assessment ◽

Mineral Density ◽

Tissue Quality ◽

Ample Evidence ◽

Increased Risk

Background: There is ample evidence that patients with CKD have an increased risk of osteoporotic fractures. Bone fragility is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in general population and CKD patients. Although bone mineral density (BMD) is a very useful clinical tool in assessing bone strength, it may underestimate the fracture risk in CKD patients. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures independently of BMD in CKD patients. Bone quality and fracture risk in CKD patients can be better assessed by utilizing new technologies such as trabecular bone score and high-resolution imaging studies. Additionally, invasive assessments such as bone histology and micro-indentation are useful counterparts in the evaluation of bone quality. Summary: A precise diagnosis of the underlying skeletal abnormalities in CKD patients is crucial to prevent further bone loss and fractures. We must consider bone quantity and quality abnormalities for management of CKD patients. Here in this part I, we are focusing on advances in bone quality diagnostics that are expected to help in proper understanding of the bone health in CKD patients. Key Messages: Assessment of bone quality and quantity in CKD patients is essential. Both noninvasive and invasive techniques for the assessment of bone quality are available.

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Mild Chronic Hyponatremia and Osteoporotic Fractures Risk in Elderly

Revista de Chimie ◽

10.37358/rc.18.12.6783 ◽

2019 ◽

Vol 69 (12) ◽

pp. 3520-3523

Author(s):

Raluca Alexandra Trifanescu ◽

Dan Soare ◽

Catalin Carstoiu ◽

Gheorghe Popescu ◽

Alina Mihaela Pascu ◽

...

Keyword(s):

Bone Mineral Density ◽

Elderly People ◽

Bone Mineral ◽

Hip Fractures ◽

Serum Sodium ◽

Odds Ratio ◽

Osteoporotic Fractures ◽

Mineral Density ◽

Chronic Hyponatremia ◽

The Relationship

Low serum sodium levels were associated with increased prevalence of osteoporosis and fractures. The aim of the study was to assess the relationship between serum sodium and bone mineral density and/or osteoporotic fractures� prevalence in elderly people. A total number of 260 patients (23 men / 237 women), aged 66.5 � 12.8 years, were retrospectively assessed. Serum sodium levels were measured in all patients. Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). Results: serum natremia was 140.3 � 4.4 mmol/L; prevalence of hyponatremia was 7.3%; frailty fractures were present in 117 out of 260 patients (45%). Patients with fractures had lower serum sodium levels as compared to patients without fractures (139 � 3.9 vs. 141.5 � 4.6 mmol/L, p [ 0.001). Patients with osteoporosis (n = 179) also showed lower natremia as compared to patients with normal BMD and osteopenia (n = 81): 139.9 � 4.7 vs. 141.2 � 3.8 mmol/L, p = 0.035. In patients admitted in the hospital for fractures (n = 92), prevalence of hyponatremia was 13.04%. Hyponatremic patients had significantly higher prevalence of fractures (73.7% vs. 42.7%, p = 0.0147) as compared to normonatremic patients. Odds ratio (OR) for fractures in patients with hyponatremia was 3.75 [95% C.I.: 1.3-10.75], p = 0.0138; OR for hip fractures in patients with hyponatremia was 3.65 [95% C.I.: 1.38-9.64], p = 0.0089. Both incidence and prevalence of hyponatremia increase with age, especially in patients treated with diuretics. Several clinical studies found an association between mild chronic hyponatremia in elderly and increased odds ratio of osteoporosis at the total and at femoral neck; the study also showed an increased odds ratio for all fractures and for hip fractures in hyponatremic patients. Elderly people at risk of osteoporotic fractures should have sodium serum measured.

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Performance of HR-pQCT, DXA, and FRAX in the discrimination of asymptomatic vertebral fracture in postmenopausal Chinese women

Archives of Osteoporosis ◽

10.1007/s11657-021-00939-0 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Meiling Huang ◽

Vivian Wing-yin Hung ◽

Tsz Kiu Li ◽

Sheung Wai Law ◽

Yulong Wang ◽

...

Keyword(s):

Vertebral Fracture ◽

Fracture Risk ◽

Postmenopausal Women ◽

Bone Quality ◽

Assessment Tool ◽

Chinese Women ◽

Quantitative Computed Tomography ◽

Areal Bone Mineral Density ◽

Mineral Density ◽

Significant Difference

Abstract Summary Volumetric bone density (vBMD) and trabecular microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) can discriminate the patients with high risk of asymptomatic vertebral fracture (VF) in postmenopausal Chinese women. These findings suggested that HR-pQCT could provide additional information on bone quality of the patients with asymptomatic VF. Introduction Although there were several studies using HR-pQCT to investigate asymptomatic VF, it remains uncertain if HR-pQCT parameters can discriminate asymptomatic VF patients, especially in Chinese population. The purpose of this study was to investigate whether bone quality measured by HR-pQCT could discriminate asymptomatic VF independent of hip areal bone mineral density (aBMD) measured by dual-energy x-ray absorptiometry (DXA) and fracture risks evaluated using built-in Fracture Risk Assessment Tool (FRAXBMD). Methods This is a nested case–control study. One hundred seventy-five ambulatory Chinese postmenopausal women aged 60–79 years were retrieved from Normative Reference Standards (NRS) cohort in Hong Kong. DXA was used to identify VF from lateral spine images (VFA) using Genant’s semi-quantitative method. Major osteoporotic fracture risk was calculated using FRAX tool. HR-pQCT was used to assess vBMD, microarchitecture, and estimated strength at both distal radius and tibia. Comparison of HR-pQCT parameters between asymptomatic VF and control was performed using covariance analysis. Logistic regression analysis was performed for calculating the adjusted odds ratio (OR) with 95% confidence intervals (CI) of fracture status as per SD decrease in HR-pQCT parameters. Results Women with asymptomatic VF were older than those of the control in our NRS cohort. Nevertheless, after adjusted for covariance, asymptomatic VF showed significantly lower trabecular vBMD (Tb.vBMD) at radius but higher SMI at tibia as compared with those of the control. Tb.vBMD at radius yielded the highest value of area under the curve (AUC) as compared with total hip aBMD and FRAXBMD. However, no significant difference was found among each other. Conclusion Tb.vBMD at the radius and SMI at the tibia provided by HR-pQCT can discriminate asymptomatic VF independent of hip aBMD and FRAXBMD by DXA in postmenopausal women.

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Bone Mineral Density At Diagnosis Determines Fracture Rate in Children Treated According to the DCOG-ALL9 Protocol

Blood ◽

10.1182/blood.v120.21.1469.1469 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1469-1469

Author(s):

Mariel L te Winkel ◽

Rob Pieters ◽

Wim C.J. Hop ◽

Jan C. Roos ◽

Inge M. van der Sluis ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Cumulative Incidence ◽

Risk Group ◽

Age At Diagnosis ◽

Fracture Rate ◽

Multivariate Linear Regression Analysis ◽

Mineral Density ◽

X Ray ◽

Increased Risk

Abstract Abstract 1469 Purpose As survival rates for pediatric acute lymphoblastic leukemia (ALL) have significantly improved, awareness of side effects such as skeletal toxicity becomes increasingly important. As BMD decrease over time might be associated with an increased risk of fractures, we performed repeated measurements of BMD in a large nation-wide study and studied the incidence of fractures in these children treated for ALL. Methods Prospectively, serial measurements (at diagnosis, after 32 weeks, after 2 years (at cessation of therapy) and after 3 years (1 year after cessation of therapy)) of bone mineral density of the lumbar spine (BMDLS) were performed in 399 ALL patients using dual energy X-ray absorptiometry (DXA). Using logistic multivariate regression, we evaluated the following putative risk factors for a low BMDLS:age at diagnosis, gender, risk group of ALL treatment, weight and height at diagnosis. Moreover, Kaplan-Meier survival analysis was used to assess the cumulative incidence of fractures in 672 patients treated with the dexamethasone-based DCOG-ALL9 protocol. All reported fractures were symptomatic, and confirmed by X-ray. Cumulative incidences of fractures for different subgroups were compared with the Log-Rank test. Results At diagnosis, mean BMDLS of ALL patients was lower than that of healthy peers (mean BMDLS= −1.10 SDS, P< 0.001), and this remained significant lower during and after treatment (8 months: BMDLS = −1.10 SDS, P< 0.001; 24 months: BMDLS = −1,27 SDS, P< 0.001; 36 months: BMDLS = −0.95 SDS, P< 0.001). Multivariate linear regression analysis showed that after correction for weight, height and gender, treatment according to the HR treatment arm and older age at diagnosis had a significant negative effect on the decline of BMDLS during treatment (high-risk group: b = −0.50, P<0.001 and age at diagnosis: b = −0.15, P<0.001). The cumulative incidence of fractures at 3 years was 17.8%. Cumulative incidences of fractures between risk groups and age groups were not significantly different (NHR 18.8% vs. HR 15.7%, P = 0.18 and <10 years 17.7% vs. ≥10 years 17.6%, P = 0.85). Patients who developed fractures had a lower BMDLS during treatment than those without fractures. Treatment-related bone loss was similar in patients without fractures and patients with fractures (respectively: Δ BMDLS = −0.12 SDS vs. Δ BMDLS= −0.36 SDS; interaction group time, P = 0.295). Conclusion This large prospective study shows that the low value of BMDLS both at diagnosis and during treatment, rather than the treatment-related decline of BMDLS, determines the markedly increased fracture risk of 17.8%. Disclosures: No relevant conflicts of interest to declare.

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