Knee joint Swelling Suggests Potentially Treatable Bone Marrow Edema

Bone marrow edema (BME) is cropping up in MRI image reports and can be harbingers of subsequent cartilage loss where it occurs – though some can progress to frank bone osteonecrosis. Clinically, the presence of knee effusion make BME 77.9% likely.

Association of Knee Effusion Detected by Physical Examination With Bone Marrow Lesions: Cross-Sectional and Longitudinal Analyses of a Population- Based Cohort
Jolanda Cibere et al
Arthritis Care & Research
Vol. 71, No. 1, January 2019, pp 39–45
https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.23575

There is talk of maybe been enlisting victims in a Bone marrow edema study but there are none active right now:
https://clinicaltrials.gov/ct2/results?cond=Bone+Marrow+Edema+Syndrome&term=&cntry=&state=&city=&dist=

 

Possible Treatments:

Strontium Ranelate -so so

Pelletier, Jean-Pierre, et al.
Disease-modifying effect of strontium ranelate in a subset of patients from the Phase III knee osteoarthritis study SEKOIA using quantitative MRI: reduction in bone marrow lesions protects against cartilage loss.
Annals of the rheumatic diseases 74.2 (2015): 422-429.
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.828.7608&rep=rep1&type=pdf

  • No Canadian DIN number yet study was done in Quebec, Canada so suspect must have been compounded.
  • “SrRan” was found to reduce bone resorption and increase formation
    strontium ranelate was given at 2 gm/day for 2-3 years from the looks of it.
  • “significantly reducing CVL  (cartilage volume loss) in the plateau and BML (bone marrow lesion) progression in the medial compartment”
  • Pain levels were different from onset :SrRan 44.5±20.0/100 vs Placebo 38.5±21.4. so made analysis more difficult.
  • Results on pain were so poor they did not publish them except to say they will able to show something on multivariate regression though said “data not shown” – tells me it has no clinical relevance pain-wise – they did admit the did not achieve some of their primary objectives

Iloprost – not really

Mayerhoefer, M. E., et al.
Short-term outcome of painful bone marrow oedema of the knee following oral treatment with iloprost or tramadol: results of an exploratory phase II study of 41 patients.
Rheumatology 46.9 (2007): 1460-1465.
https://academic.oup.com/rheumatology/article/46/9/1460/1790006

  • No Canadian DIN number
  • 50 µg of iloprost clathrate (Schering AG, Berlin, Germany) three times daily on days 1–3; after day 3, individual dose adjustment was allowed (range: 50 µg twice daily up to 2 × 50 µg three times daily).
  • The oral extended-release formulation of iloprost was developed to mimic the plasma concentration time curve of intravenous iloprost during a 6 h infusion at a dose rate of 1.5 ng/kg/min.
  • Conclusion- The analgesic effect of iloprost and tramadol was similar. BME regression on MR images was more pronounced under iloprost treatment.

Zoledronic Acid – no

Laslett, Laura Louise, et al.
Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial.
Annals of the rheumatic diseases 71.8 (2012): 1322-1328.
https://ard.bmj.com/content/71/8/1322.short

  • aged 50–80 years (n=59)
  • clinical knee osteoarthritis and knee BML (bone marrow edema)
  • Single infusion of  Zoledronic acid 5 mg/100 mlResults:

zoledronic_BME

  • No Canadian DIN number
  • Results were mediocre and standard deviation bars are not apart so I see no real significant difference
  • I call this a MORON study  –  as seen from pamidronate study below, and previous pamidronate studies on compression fractures of spine, it took THREE infusions to get good results – I also call them ONE-SHOT-WONDERS
    so possible could have got results with THREE infusions

a repeat of this study was done and showed No benefit

Zoledronic acid infusions had no effect  on knee osteoarthritis with bone marrow edema lesion:
Cai, G., et al.
OP0016 A multicentre randomised controlled trial of zoledronic acid for osteoarthritis of the knee with bone marrow lesions.
(2018): 57-58.
https://ard.bmj.com/content/77/Suppl_2/57.2

  • 5 mg/100 mls iv yearly

no benefit

 


In actual knee osteonecrosis:

Kraenzlin, Marius E., et al.
Possible beneficial effect of bisphosphonates in osteonecrosis of the knee.
Knee surgery, sports traumatology, arthroscopy 18.12 (2010): 1638-1644.
http://doc.rero.ch/record/319972/files/167_2010_Article_1106.pdf

  • pamidronate 120 mg i.v. divided in 3–4 perfusions over 2 weeks
  • followed by oral bisphosphonate treatment with alendronate 70 mg weekly for 4–6 months.
  • results in pain relief :  “VAS decreasing from 8.2 ± 1.2 at baseline to 5.02 ± 0.6 after 4–6 weeks (P<.001). After 6 months, the VAS decreased by 80% ( p <0.001).”

 

Not all studies were positive:

Meier, C., et al.
Effect of ibandronate on spontaneous osteonecrosis of the knee: a randomized, double-blind, placebo-controlled trial.
Osteoporosis international 25.1 (2014): 359-366.
https://link.springer.com/article/10.1007/s00198-013-2581-5

  • “participants were randomized to receive 13.5 mg ibandronate (Bonviva IV; Roche Pharma AG, Switzerland) or placebo intravenously divided in four injections within
    2 weeks (once 1.5 mg then 3 mg per injection) and followed by a fifth injection after 3 months (3 mg).”
  • “no beneficial effect over and above anti-inflammatory medication”

 

For patellar bone marrow edema,  the The Formfit Knee Hinged Lateral J  support showed benefit after 6 weeks:

Callaghan, Michael J., et al.
A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions.”
Annals of the rheumatic diseases 74.6 (2015): 1164-1170.
https://ard.bmj.com/content/74/6/1164

 

BMEpatellar support

https://www.ossur.co.uk/injury-solutions/products/knee/knee-sleeves-wraps/form-fit-knee-hinged-lateral-j

Results:
bracing_bme_patella

Well, not going to be running any time soon with bracing…

Biphosphonates on OA

 

Interestingly biphosphonates were found to help knee OA pains in first 3 years of use:
Laslett, Laura L., et al.
Effect of bisphosphonate use in patients with symptomatic and radiographic knee osteoarthritis: data from the Osteoarthritis Initiative.
Annals of the rheumatic diseases 73.5 (2014): 824-830.
http://eprints.whiterose.ac.uk/89937/3/Laslett%20et%20al_manuscript%20including%20figures.pdf

biphosphonates_kneeoa

 

Alendronate 35 mg/wk reduced hip OA pains but failed to help AO pregression:

Nishii, Takashi, et al.
Alendronate treatment for hip osteoarthritis: prospective randomized 2-year trial.
Clinical rheumatology 32.12 (2013): 1759-1766.
https://link.springer.com/article/10.1007/s10067-013-2338-8

alendronate_hipoa

I can’t make any sense of that study – subjects were not matched for pain at start and it went downhill from there.

 

Comment – up until now I have not written up bone marrow edema as no treatment seemed worth writing up. I am forced to admit it might not have changed much

 

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