Monday, February 16, 2015

Bisphosphonates - By Dr. Ian Muldowney


Bone tumors are relatively common tumors in dogs, specifically primary bone tumors such as osteosarcoma.  However, secondary bone involvement  with , multiple myeloma, histiocytic sarcoma, apocrine gland anal sac adenocarcinomas and transitional cell carcinomas, are also commonly observed in veterinary practice.1  Because of the intense and often chronic pain caused by focal bone destruction and the  decrease in quality of life, amputation remains the treatment of choice for local control of appendicular bone tumors.2  However, amputation is not an option for every patient.  Profound preexisting orthopedic or neurologic disease may prohibit a dog from functioning acceptably with only  three  limbs.  In addition, some pet owners do not have the financial recourses to pursue aggressive surgery while others find the idea of amputation anathema.   For all of these reasons, a palliative approach is often pursued.   

Palliative treatment aims to alleviate the  bone pain associated with the tumor. Bone pain from skeletal tumors develops by two mechanisms:  first, as the malignant osteoblasts rapidly proliferate, normal stromal cells stimulate nociceptors, which are found at highest concentrations in the periosteum, leading to the sensation of pain.  Second, continuous pain stimulation is maintained by the chronic dysregulation of bone resorption by osteoclasts.3, 6

Because of the multimodal genesis of bone cancer pain, many patients remain refractory to traditional oral and transdermal analgesics.  The use of bisphosphonate therapy is becoming increasingly more common in veterinary oncology.  Bisphosphonates are synthetic analogues of pyrophosphates that have an affinity for bone mineral and decrease pain by inhibiting reabsorption of bone by osteoclasts.  These molecules interfere with normal intracellular signaling mediated by GTP-binding proteins and cause disruption of cellular interactions with the extracellular matrix, thus leading to apoptosis of osteoclasts. 4 
While many bisphosphonates are commercially available, two of the more commonly used bisphosphonates in veterinary medicine are pamidronate and zoledronate.  Both are administered as an intravenous infusion up to every twenty-eight days and have been demonstrated to maintain analgesic effects for up to four months.5,6,7  While these infusions are largely well tolerated, mild gastrointestinal toxicity and, rarely, renal insufficiency have been reported. 2,6 

Overall, bisphosphonates remain a relatively safe and effective treatment for alleviating pain and improving quality of life in dogs with bone tumors. Oral bisphosphonate therapy is not routinely indicated in dogs as esophageal irritation is a common sequelae. People are advised to remain vertical for 60 minutes after taking any oral bisphosphonate. The horizontal orientation of the esophagus in dogs and cats versus the vertical orientation of the esophagus in a standing person preclude this recommendation for veterinary patients.


Dr. Ian Muldowney


References
1.  Fan, et al.  Evaluation of Intravenous Pamidronate Administration in 33 Cancer-Bearing Dogs with Primary or Secondary Bone Involvement.  J Vet Intern Med 2005;19:74–80.
2.  Kozicki AR, et al.  Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma.  Veterinary Comparative Oncology 2013.
3.  Goblirsch MJ, et al.  Biology of bone cancer pain.  Clinical Cancer Research, 12: 6231-6235, 2006.
4.  Gourion-Arsiquaud S, et al.  Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity.  Bone,  2010; 46: 666-672.
5.  Poirier VJ, et al.  The bisphosphonates alendronate and zoledronate are inhibitors of canine and human osteosarcoma cell growth in vitro.  Veterinary Comparative Oncology 2003; 1: 207–215.
6.  Fan, et al.  Single-Agent Pamidronate for Palliative Therapy of Canine Appendicular Osteosarcoma Bone Pain.  J Vet Intern Med, 2007;21:431-439.
7.  Fan, et al.  Double-Blind Placebo-Controlled Trial of Adjuvant Pamidronate with Palliative Radiotherapy and Intravenous Doxorubicin for Canine Appendicular Osteosarcoma Bone Pain.  J Vet Intern Med 2009;23:152–160.

25 comments:

  1. I was diagnosed with bone cancer, I am 36 year old male which makes this Mine was a high rate. and I have been in hell‎ having pains everyday swelling and rashes in my left leg, and also affected all over my body I have been on a sick bed I almost got disfigured from the bone cancer I've had lot treatment if I would be able to meet up my with life even the Dr's don't no about my pains I was going through. Not on till I was recommended to a herbalist Dr online. last treatment I applied was the natural herbal medicine from Dr galiga herbal centre which finally healed me out from bone cancer, I can easily work and ran with my two legs. My post goes to every patients whom have be diagnosed with cancer. Here is the African herbalist email address i got healed with his natural herbal treatments drgaligaherbalcenter@gmail.com

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  4. 5 years ago I had warts, I was treated with some liquid applied to the warts they continued to grow and spread... The next 2 doctors did laser surgery to remove them. 1 year after the surgery, they grew back close to where the 1st ones were' so I was finally told it was hpv. I have had it for very long time, I contract it from my cheated boyfriend and I found out he was also infected and I end up the relationship between us. the warts was so embarrasses because it started spreading all over I have be dealing with this things for very long time the last treatment I take was About 2 years ago I applied natural treatment from Dr onokun herbal cure, a week after applying the treatment all the warts was gone. it's now 2 years and some months I don't have single wart or any symptoms of hpv. wow"" it's great, Dr onokun has finally cured me. Anyone living with hpv contact Dr onokun for natural treatment.
    His email address: dronokunherbalcure@gmail.com‎ or whatsapp him +2349064844957

    ReplyDelete
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  6. i Thank God will continue to bless you more abundantly, for the good works you are doing in peoples life, I will keep on writng and posting testimonies about you on the Internet, I’m jennifer I was a HPV patient, I saw a blog on how Dr. omohan cured someone, I contacted him and also got my healing, kindly email him now on dromohanherbalmedicine@gmail.com or whatsapp him +2348164816038 God we bless you

    ReplyDelete
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  8. i was diagnose with genital warts,last six months which finally shows out! i had hpv. for very long time i suffered for the virus and i was told there is no hpv cure. except treatment to control it i just fill killing my self because there was no hope all i could think loosing my life because it was so embarrass for been hpv patient. about few weeks ago i read possible natural cure on line which was guarantee and i purchased it. after two weeks taking herbal treatment the hpv got eliminated by killing all symptoms and the warts in my genital area disappeared. it so amazing i got ride to the hpv. i so much like to shear this testimony to every article for others living with hpv there is possible natural herbs to eliminate it. email Dr onokun for help. his herbal clinic address; dronokunherbalcure@gmail.com

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  9. i got hpv from my boyfriend  and i was trying all i could do to get rid of this virus over 4 months now i have taking a lot of drugs from different medical doctor which didn't work at all, last month i was doing some research on google on how to get cured totally from this virus i found someone testimony on how she got cured totally from hpv with the help of doc. onokun  natural herbs and she drop doc onokun email address, So i decide to give him a try and i contact him for help he told how to purchase the natural herbs and i did that, Do you believe i only took this herbs for 2 weeks and i got cured permanently from the hpv virus without no side effect. Thank you so much doc onokun for the help i will make sure i tell the whole world about you. contact him if you need his help too  via: Dronokunherbalcure@gmail.com 

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  10. I contracted hpv from my ex partner we broke up the relationship about four years ago, I has been on treatment for some years, I had lot pains and embarrassment for been hpv patient last two month i did hpv research online and found website for natural treatment to get ride of my infection, and i went through the site and recommend me to Dr onokun I contacted Dr onokun through his website and been his patient after one month I got cured. I want everyone living with hpv to get this treatment and got cured Dr onokun have the cure to every virus. his email; dronokunherbalcure@gmail.com

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  14. I Want To Appreciate Dr.OYAGU for hs great deeds, I Was Diagnosed With type 2 Herpes Virus Last year,And Was Look For Solution To Be Cured Luckily I Saw Testimonies On How Dr.OYAGU Cure Herpes Virus I Decided To Contact Dr.OYAGU I Contacted Him He Prepared A Herbal Medicine Portion And Sent It To Me,I Started The Herbal Medicine For My Health.He Gave Me Step By Step Instructions On How To Apply It, When I Applied It As Instructed, I Was Cured Of This Deadly Herpes Within 2 weeks, I Am Now Herpes Negative.My Brother And Sister I No That There Are So Many People That Have There Same Herpes Virus Please contact Dr OYAGU To Help You Too,And Help Me To Thank Dr.OYAGU For Cure Me, I’m Cured By Dr. OYAGU Herbal Medicine,His Contact Email:oyaguspellcaster@gmail.com

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  15. I Want To Appreciate Dr.OYAGU for hs great deeds, I Was Diagnosed With type 2 Herpes Virus Last year,And Was Look For Solution To Be Cured Luckily I Saw Testimonies On How Dr.OYAGU Cure Herpes Virus I Decided To Contact Dr.OYAGU I Contacted Him He Prepared A Herbal Medicine Portion And Sent It To Me,I Started The Herbal Medicine For My Health.He Gave Me Step By Step Instructions On How To Apply It, When I Applied It As Instructed, I Was Cured Of This Deadly Herpes Within 2 weeks, I Am Now Herpes Negative.My Brother And Sister I No That There Are So Many People That Have There Same Herpes Virus Please contact Dr OYAGU To Help You Too,And Help Me To Thank Dr.OYAGU For Cure Me, I’m Cured By Dr. OYAGU Herbal Medicine,His Contact Email:oyaguspellcaster@gmail.com

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  16. I Want To Appreciate Dr.OYAGU for hs great deeds, I Was Diagnosed With type 2 Herpes Virus Last year,And Was Look For Solution To Be Cured Luckily I Saw Testimonies On How Dr.OYAGU Cure Herpes Virus I Decided To Contact Dr.OYAGU I Contacted Him He Prepared A Herbal Medicine Portion And Sent It To Me,I Started The Herbal Medicine For My Health.He Gave Me Step By Step Instructions On How To Apply It, When I Applied It As Instructed, I Was Cured Of This Deadly Herpes Within 2 weeks, I Am Now Herpes Negative.My Brother And Sister I No That There Are So Many People That Have There Same Herpes Virus Please contact Dr OYAGU To Help You Too,And Help Me To Thank Dr.OYAGU For Cure Me, I’m Cured By Dr. OYAGU Herbal Medicine,His Contact Email:oyaguspellcaster@gmail.com

    Or Cell Whatsapp Number +2348101755322 thank you .....

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  17. I'm 61 years old, I contracted hpv in 2011' I has be taking lot treatment for it and embarrassedsome months ago the wart stated coming out seriously, I used lot recommendation because there was lot warts around my anus and was so . but today I'm totally happy I got the virus eliminated by using natural treatment from Dr Onokun herbal center after his treatment I got cured. all the warts went away' seriously believed Dr Onokun he have the cure for human papillomavirus because he has eliminated hpv been in my body since 2011, Dr Onokun make it possible for me. Here is Dr Onokun email to reach him: Dronokunherbalcure@gmail.com  he is welled capable of curing terrible diseases.  

    ReplyDelete
  18. I Want To Appreciate Dr.OYAGU for hs great deeds, I Was Diagnosed With type 2 Herpes Virus Last year,And Was Looking For Solution To Be Cured Luckily I Saw Testimonies On How Dr.OYAGU Cure Herpes Virus I Decided To Contact Dr.OYAGU I Contacted Him He Prepared A Herbal Medicine Portion And Sent It To Me,I Started The Herbal Medicine For My Health.He Gave Me Step By Step Instructions On How To Apply It, When I Applied It As Instructed, I Was Cured Of This Deadly Herpes Within 2 weeks, I Am Now Herpes Negative.My Brother And Sister I No That There Are So Many People That Have There Same Herpes Virus Please contact Dr OYAGU To Help You Too,And Help Me To Thank Dr.OYAGU For Cure Me, I’m Cured By Dr. OYAGU Herbal Medicine,His Contact Email;Oyaguherbalhome@gmail.com

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    ReplyDelete
  19. I found out, that taking herbal treatment is the best to get rid of hpv as soon as i feel the symptoms of hpv is appearing, i took the healing process by contacting Dr onokun for natural treatment it works wonders, amazingly ever since I had the herbal treatment i have not feel these horrible disease anymore and my doc told me the virus is gone, i am glad i finally got cured out from this horrible disease. every hpv or herpes patients should also get in touch with this herbalist Dr to get ride of these disease forever his email address; Dronokunherbalcure@gmail.com 

    ReplyDelete
  20. I'm 61 years old. I contracted hpv in 2011' I has be taking lot treatment for it and embarrassed some months ago the wart stated coming out seriously, I used lot recommendation because there was lot warts around my anus and was so . but today I'm totally happy I got the virus eliminated by using natural treatment from Dr Onokun herbal center after his treatment I got cured. all the warts went away' seriously believed Dr. Onokun he have the cure for human papillomavirus because he has eliminated hpv been in my body since 2011, Dr. Onokun make it possible for me. Here is Dr. Onokun email: Dronokunherbalcure@gmail.com or page at: https://www.facebook.com/naturaltreatmentcenter1 or WhatsApp him via +1 ( 323 ) 689 3594 he is welled capable of curing terrible diseases.

    ReplyDelete



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