Neridronate in bone marrow edema syndrome. Efficacy and safety of two therapeutic regimens

The bone marrow edema syndrome (BMES) is a severely disabling pain syndrome without a definite treatment and refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip, regional migratory osteoporosis, and reflex sympathetic dystrophy. Magnetic resonance imaging is used for early diagnosis and monitoring of its progression. Early differentiation from other aggressive conditions with longterm sequelae is essential in order to avoid unnecessary treatment. The aim of this monocentric trial was to test the efficacy and the safety of amino-bisphosphonate neridronate administered in two different regimens in patients with BMES. 192 patients with BMES secondary to osteoarthritis localized in the knee, hip, wrist or foot were randomly assigned to intravenous (iv) infusion of 100 mg neridronate given four times over 10 days (Group A, 72 subjects) or alternatively to iv infusions of 100 mg every 21 days over 3 months (Group B, 120 subjects). Magnetic resonance image (MRI) was performed at baseline and after 180 days. We assessed a 0-100 mm pain visual analogue scale (VAS) in each patient, too. Outcomes were MRI changes and VAS changes. A control group (35 patients) was enrolled too, treated conservatively with non-steroidal anti-inflammatory drugs and articular rest. We observed a significant improvement in MRI with the resolution of bone marrow lesions present at the baseline (P<0.01), without a significant difference between Group A and Group B. The VAS score decreased significantly during the study in both groups (P<0.05) without a significant difference between the two treatment groups (P>0.1). Both groups showed a significant clinical and radiologic improvement compared with the control group (P<0.001). In patients with BMES, the infusions of neridronate 100 mg every 21 days over 3 months or alternately every 3 days over 10 days were associated with clinically relevant and persistent benefits without significant differences between the two treatment schedules. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice in BMES.

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THU0463 EFFICACY AND SAFETY OF NERIDRONATE IN BONE EDEMA SYNDROME

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4353 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 468.2-469

Author(s):

A. M. Lurati ◽

A. Laria ◽

P. Faggioli ◽

L. Castelnovo ◽

A. Tamburello ◽

...

Keyword(s):

Bone Marrow ◽

Pain Syndrome ◽

Conclusive Evidence ◽

Control Group ◽

Transient Osteoporosis ◽

Regional Migratory Osteoporosis ◽

Significant Difference ◽

Bone Edema ◽

Group A ◽

Group B

Background:Bone Marrow Edema Syndrome (BMES) is a severely disabling pain syndrome without a definite treatment and refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). Magnetic resonance imaging is used for the early diagnosis and monitoring the progression of the disease. Early differentiation from other aggressive conditions with long-term sequelae is essential in order to avoid unnecessary treatment.Objectives:Aim of this monocentric trial was to test the efficacy and the safety of the amino-bisphosphonate neridronate in patients with BMES administered in two different regimens.Methods:192 patients with BMES secondary to osteoarthritis localized to knee, hip, wrist or foot were randomly assigned to I.V. infusion of 100 mg neridronate given four times over 10 days (Group A, 72 subjects) or alternatively to I.V. infusions of 100 mg every 21 days over 3 months (Group B, 120 subjects). At baseline and after 180 days we performed an MRI. We assessed a 0-100 mm pain VAS in each patient, too. Outcomes were to evaluate the MRI changes and the VAS changes. A control group (35 patients) was enrolled too, treated conservatively with NSAIDs and articular rest.Results:we observed a significant improvement in MRI with the resolution of bone marrow lesions present at the baseline (p<0.01), without a significant difference between Group A and Group B. Visual analogue scale (VAS) score decreased significantly during the study in both groups (p<0.05) without a significant difference between the two treatment groups (p>0.1). Both groups showed a significant clinical and radiologic improvement compared with control group (p<0.001).Conclusion:In patients with BMES, the infusions of neridronate 100 mg every 21 days over 3 months or alternately every 3 days over 10 days are associated with clinically relevant and persistent benefits without significant differences between the two treatment-schedules. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice BMES.Disclosure of Interests: :None declared

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Bone Marrow Transplantation or G-CSF Treatment Can Accelerate Recovery of Injured Spinal Cord in Mice.

Blood ◽

10.1182/blood.v104.11.4181.4181 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4181-4181

Author(s):

Damianos Sotiropoulos ◽

Eleni Siotou ◽

Evangelia Athanasiou ◽

Christos Kalpouzos ◽

Panayotis Kaloyannidis ◽

...

Keyword(s):

Spinal Cord ◽

Bone Marrow ◽

Bone Marrow Cells ◽

Control Group ◽

Significant Difference ◽

Cord Injury ◽

Group A ◽

B Mice ◽

The Mean ◽

Group B

Abstract Mice, unlike rats and humans, have a self recovery mechanism of spinal cord injury. Whether the hematopoietic system is involved in this mechanism is under investigation. In this study we tested whether bone marrow cells transplanted or mobilized by a growth factor in mice with spinal cord injury, can accelerate the recovery. C57bl/6 female mice 10 to 12 weeks of age underwent spinal cord incision in an open operation. The injury was performed as a complete transection including the dura mater and the whole circumference of the cord at the T10-T11 intervertebral space with a micro scalpel (No 11). Group A mice received 200μg/kg/day G-CSF subcutaneously for 7 days, starting 24 hours after operation. Group B mice received 106 light density bone marrow cells from C576bl/6 donor mice intravenously 24 hours after operation. Control group mice received no treatment. Histological evaluation was performed at 48 hours, 1 week, 3 weeks and 5 weeks postoperatively. Paraffin embedded longitudinal samples of spinal cord were cut as serial sections. Spinal cord damage was estimated by measuring the maximum diameter of the area of axonal damage and disruption of astrocytic network using immunostaining for neurofilaments and GFAP. Antibodies against CD68 were applied to identify macrophage aggregations. All measurements were performed by morphometric photo analysis. The volume of fibroblastic infiltration was estimated using a grading system (0–7), based on Van Gieson stain for connective tissue. Functional deficits and recovery over time were evaluated by testing hind limb reflex and coordinated motor function (Kuhn and Wrathal functional tests, modified by Seki et al, 2002). All tests have been videotaped. Outcome scores at 48 hours, 1 week, 3 weeks and 5 weeks postoperatively for the control group, group A and group B mice were analyzed with the Mann-Whitney U test. 48 hours post operatively all mice in all groups were paralyzed in both hind limbs. Gradual improvement was observed in all groups. At week 3 there was a significant difference between the mean scores of functional tests for both treated groups (A and B) compared with the mean scores of the control group. Statistically significant difference (p<0,05) was observed in 5 out of 7 tests for group A and in 3 out of 7 tests for group B. Same difference between Group A mice and control group mice was observed by 5 weeks, while group B had no statistically significant difference. No animal in any of the groups had a complete recovery 5 weeks postoperatively. Spinal cord in control group mice showed a gradually increase of fibroblastic infiltration until 5 week which entirely separated the two ends of the cord. In group A and group B mice a significant decrease of fibroblastic infiltration was observed at week 5 compared with week 3. Macrophage aggregations were evident at weeks 1 and 5 but not at week 3 in all groups. In conclusion our results indicate that light density bone marrow transplanted cells or G-CSF treatment can accelerate spinal cord injured mice recovery. It is possible that this is associated with a decrease in fibroblastic infiltration of spinal cord. Macrophage aggregation may also play an important role in the mechanism of recovery in mice, while in rats a different reaction including cavitation and delayed demyelination prohibits neurological recovery.

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MRI Findings in the Subchondral Bone Marrow: A Discussion of Conditions Including Transient Osteoporosis, Transient Bone Marrow Edema Syndrome, SONK, and Shifting Bone Marrow Edema of the Knee

Seminars in Musculoskeletal Radiology ◽

10.1055/s-2006-957171 ◽

2006 ◽

Vol 10 (3) ◽

pp. 177-186 ◽

Cited By ~ 36

Author(s):

Holly Gil ◽

Scott Levine ◽

Adam Zoga

Keyword(s):

Bone Marrow ◽

Subchondral Bone ◽

Bone Marrow Edema ◽

Transient Osteoporosis ◽

Mri Findings ◽

Bone Marrow Edema Syndrome ◽

Transient Bone Marrow Edema ◽

Marrow Edema

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Letter to Editor - A Clinical ‘PIC- Perspectives, issues & Concerns” on Idiopathic Transient Osteoporosis during Pregnancy with alarm bells on its Idiopathic nature - Response

Journal of Orthopaedic Case Reports ◽

10.13107/jocr.2021.v11.i01.1990 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sharat Agarwal

Keyword(s):

Bone Marrow ◽

Bone Marrow Edema ◽

Transient Osteoporosis ◽

Bone Marrow Edema Syndrome ◽

Labral Tears ◽

Transient Bone Marrow Edema ◽

Bone Marrow Edema Pattern ◽

Magnetic Resonance Imaging Mri ◽

Articular Pathology ◽

Marrow Edema

Dear Editor, At the outset, I would like to congratulate the authors of the article published in your journal in the current issue entitled- Idiopathic Transient Osteoporosis during Pregnancy – Report of a Clinical Case JOCR November – December 2019 Volume 9 Issue 6 Page 54-57. However, I regret to mention that the workup mentioned in this article needs to be improved, before one can come to definitive diagnosis of Idiopathic Transient Osteoporosis during Pregnancy. I would like to highlight various perspectives, issues & concerns, the knowledge of which are must for the readers of this journal pertaining to this disorder. It is pertinent to mention no doubt the increasing utilization of magnetic resonance imaging (MRI) has allowed physicians to investigate edematous changes in bone marrow, a clinically important entity which was previously undetected on conventional radiographs. The first use of the term “bone marrow edema” was by Wilson et al in 1988, and the term “bone marrow edema syndrome” was described in 1993 after the investigation of histological specimens [1]. Later on, importantly Hayes et al. advocated that the term “transient bone marrow edema syndrome” should be used for patients in whom the bone marrow edema pattern was not accompanied by radiographic evidence of osteopenia [2]. And thus separating the two entities i.e. “the transient bone marrow edema syndrome” and “Transient Osteoporosis” Occurrence of hip pain during pregnancy is quite common, although transient osteoporosis as a condition causing this symptom is uncommonly seen. Clinicians should also be aware of intra-articular disorders such as loose bodies, and labral tears; peri-articular pathology such as tendinitis and bursitis; or extra-articular conditions such as referred pain from the lumbar spine, the sacroiliac joint, and or from nerve entrapment syndromes. So, a detailed history and physical examination is helpful to narrow the differential diagnoses, which, in turn, dictate the modal

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Transient Bone Marrow Edema Syndrome of the Knee: Clinical and Magnetic Resonance Imaging Results at 5 Years After Core Decompression

Arthroscopy The Journal of Arthroscopic and Related Surgery ◽

10.1016/j.arthro.2006.04.095 ◽

2006 ◽

Vol 22 (8) ◽

pp. 866-871 ◽

Cited By ~ 35

Author(s):

Christian E. Berger ◽

Andreas H. Kröner ◽

Karl-Heinz Kristen ◽

Georg F. Grabmeier ◽

Rainer Kluger ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Bone Marrow ◽

Magnetic Resonance ◽

Bone Marrow Edema ◽

Core Decompression ◽

Resonance Imaging ◽

Bone Marrow Edema Syndrome ◽

Imaging Results ◽

Transient Bone Marrow Edema ◽

Marrow Edema

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The efficacy and safety of bisphosphonates in patients with bone marrow edema syndrome/transient osteoporosis: A systematic literature review

Journal of Orthopaedics ◽

10.1016/j.jor.2020.11.011 ◽

2020 ◽

Vol 22 ◽

pp. 592-597

Author(s):

Athanasios N. Ververidis ◽

Konstantinos Paraskevopoulos ◽

Anthimos Keskinis ◽

Georgios I. Petkidis ◽

Konstantinos Tilkeridis

Keyword(s):

Bone Marrow ◽

Literature Review ◽

Systematic Literature Review ◽

Bone Marrow Edema ◽

Transient Osteoporosis ◽

Efficacy And Safety ◽

Bone Marrow Edema Syndrome ◽

Marrow Edema

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Transient Osteoporosis and the Bone Marrow Edema Syndrome (BMES)

Bisphosphonates in Medical Practice ◽

10.1007/978-3-540-69870-8_15 ◽

2007 ◽

pp. 143-149

Keyword(s):

Bone Marrow ◽

Bone Marrow Edema ◽

Transient Osteoporosis ◽

Bone Marrow Edema Syndrome ◽

Marrow Edema

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The evaluation of bone marrow edema in sacroiliac joint in patients with ankylosing spondylitis using magnetic resonance imaging Dixon sequence

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04716-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ming-Shan Du ◽

Xuan-Qi Xiong ◽

He Liu ◽

Xin Qin ◽

Xiao-Fei Hu ◽

...

Keyword(s):

Bone Marrow ◽

Ankylosing Spondylitis ◽

Magnetic Resonance ◽

Sacroiliac Joint ◽

Bone Marrow Edema ◽

Control Group ◽

Case Group ◽

Resonance Imaging ◽

Sacroiliac Joints ◽

Marrow Edema

Abstract Background Bone marrow edema of the sacroiliac joint is the early imaging manifestation, an indicator of inflammatory activity of ankylosing spondylitis (AS) (Yang R, et. al. Medicine (Baltimore) 98:e14620, 2019). Objective The aim of the study was to investigate the value of magnetic resonance imaging (MRI) Dixon sequence in the diagnosis of marrow edema of the sacroiliac joint in patients with AS. Methods Forty-five patients with AS admitted in our hospital between November 2016 and February 2019 were selected retrospectively as the case group. Forty-five healthy subjects recruited between November 2016 and February 2019 served as the control group. Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were recorded after admission to the hospital. The Dixon sequence water-fat ratio of the iliac and sacral surfaces of the bilateral sacroiliac joints in the study group were compared with indicators above in order to find the correlation. Results The water-fat ratio under the bilateral sacroiliac joints on Dixon sequence images in the case group was significantly higher than that in the healthy control group (P<0.05). The Dixon sequence water-fat ratio of the iliac and sacral surfaces of the bilateral sacroiliac joints in the study group were positively correlated with spinal arthritis research (SPARCC), BASFI and BASDAI score (all P < 0.05), but did not correlate with ESR and CRP. Conclusion The water-fat ratio of magnetic resonance Dixon sequence can be used as a reference index to evaluate the degree of bone marrow edema in active stage of sacroiliac arthritis.

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