1: Spine. 2005 Nov 15;30(22):2516-22.Click here to read Links
Alendronate inhibits spine fusion in a rat model.

Hospital for Special Surgery, New York, New York 10021, USA. huangr@hss.edu

STUDY DESIGN: A posterolateral lumbar fusion model in rats.
OBJECTIVE: To study the effects of alendronate on posterolateral lumbar fusion in rats.

SUMMARY OF BACKGROUND DATA: To our knowledge, there are no studies that show a significant inhibition of manual palpation-assessed spine fusion by alendronate.

METHODS: A total of 75 Sprague-Dawley rats underwent intertransverse fusion with 7-tailbone autograft at L4-L5. Animals received saline (control), alendronate equivalent to human dose (dose1, 5 microg/kg/day), or 10 times the human dose (dose10, 50 microg/kg/day) via subcutaneous osmotic pumps starting the day of surgery. Eight weeks after surgery, animals were euthanized, and fusion was assessed by manual palpation. Radiographic area and optical density of fusion masses were calculated. Histomorphometry was used to assess the percentage area of fusion masses occupied by bone or marrow tissues. RESULTS: Manual palpation fusion rates were lower in alendronate groups (50% and 40%, respectively) than in the control group (95%, P = 0.002). Interobserver and intraobserver kappa values were high (0.97-1.00). There were dose-dependent and statistically significant (P < 0.001) increases in fusion mass area and optical density with increasing alendronate dose. Fusion masses in dose10 animals had significantly higher percent area of bone tissue (P = 0.01) and lower percent area of marrow elements (P < 0.001) when compared to control animals.

CONCLUSIONS: Alendronate inhibits spine fusion in rats. Fusion masses in alendronate-treated animals appeared radiographically larger and denser than those in control animals despite lower fusion rates. Quantitative histomorphometry confirmed that alendronate inhibited bone graft resorption and incorporation. We recommend that patients undergoing spine arthrodesis should not take alendronate until fusion is achieved.

PMID: 16284589 [PubMed - indexed for MEDLINE]
Spine. 2005 May 15;30(10):1116-21.Click here to read Links
The influence of alendronate treatment and bone graft volume on posterior lateral spine fusion in a porcine model.
* Orthopedic Department, Institute for Experimental Clinical Research, Aarhus, Denmark. xueqingyun@hotmail.com

STUDY DESIGN: An experimental animal study with randomized, paired control design was conducted using a porcine model.

OBJECTIVES: The aim of this study was to evaluate the influence of alendronate treatment and the significance of different amounts of bone graft on posterior lateral spine fusion.

SUMMARY OF BACKGROUND DATA: Treatment with bisphosphonates inhibits osteoclast-induced bone resorption and increases bone quality and density. It has been widely used clinically for treatment of osteoporosis. Bisphosphonates have been reported to elongate the callus remodeling process during fracture healing. Bisphosphonate treatment may modify bone graft healing and the remodeling process in spine fusion. The bone resorption phase exists during the healing process. Extensive bone graft resorption could reduce the basis for new bone formation, which could be an important factor for failure of spine fusion. Furthermore, different amounts of initially applied bone graft may influence spine fusion rate and bone graft incorporation process.

METHODS: Twenty-two pigs were included in the study. Eleven pigs in the treatment group received alendronate 10 mg/day p.o. for 3 months after surgery. The other 11 pigs received no bisphosphonate and served as control group. Posterior lateral fusion with the CD Horizon system was performed on the lumbar spine using different amounts of autograft (4 g on one side and 8 g on the other side) in all animals. The fusion was evaluated using radiograph, CT scan, and histomorphometry at 3 months after operation.

RESULTS: There was no statistical difference in either fusion rate or fusion mass volume between the two groups. The fusion rate based on radiograph was 75% on the 8-g autograft side and 45% on the 4-g side (P < 0.05). The mean volume of fusion mass was 2.36 cm3 on the 4-g side and 3.29 cm3 on the 8-g side (P < 0.01). No difference was found in either trabecular bone volume or fusion rate between treatment and control groups using histologic evaluation.The treatment group showed a higher fibrous tissue volume(P < 0.05), higher proportion of woven bone structure(P < 0.001), and lower bone marrow volume (P = 0.088) in the fusion mass. Different amounts of bone graft did not change the tissue composition of the fusion mass.

CONCLUSIONS: Alendronate treatment in this study decreased fusion mass remodeling without inhibiting fusion rate. Increased amounts of autologous bone graft could improve the fusion rate in this experimental spine fusion study.

PMID: 15897823 [PubMed - indexed for MEDLINE]

: Spine J. 2004 Jan-Feb;4(1):36-43. Links
The effect of alendronate sodium on spinal fusion: a rabbit model.

Department of Orthopaedic Surgery and Rehabilitation, Walter Reed Army Medical Center, Washington, DC 20307, USA. Ronald.Lehman@NA.AMEDD.ARMY.MIL

BACKGROUND CONTEXT: Bisphosphonates affect bone remodeling and increase bone mass through the inhibition of osteoclasts. Their effect on osteoblasts, and the balance between osteoblastic and osteoclastic activity on bone turnover and healing, is not completely understood. Specifically, the effect of bisphosphonates on spinal fusion has yet to be determined. With the increasing use of bisphosphonates in the elderly population, this effect needs to be delineated.

PURPOSE: To evaluate the effect of alendronate sodium after an intertransverse process spinal fusion in a rabbit model.

STUDY DESIGN/SETTING: Randomized double-blinded in vivo study of the effect of alendronate sodium in a spinal fusion model.

METHODS: Fifty New Zealand white rabbits underwent a posterolateral L5-L6 intertransverse process arthrodesis with autogenous iliac crest bone graft. The rabbits were then randomly divided into two groups. Group I received 3 cc of saline placebo per oral gavage, and Group II received 200 micrograms (approximately 0.05 mg/kg/day) of alendronate sodium dissolved in 3 cc of saline per day for 8 weeks. Upon completion, the rabbits were sacrificed and the lumbar spines harvested, radiographed and graded for motion across the fusion site with manual palpation. Two independent pathologists then prepared and sectioned each left and right fusion mass. Three random x10 fields were examined and graded for both the cephalad and caudad ends of each section (516 fields). Fusion quality was graded using an established histological scoring scale (score 0 to 7 based on fibrous and bone content of the fusion mass).

RESULTS: Two rabbits died on the day of operation, and 48 rabbits survived the operation. Five additional rabbits died within the first 2 postoperative weeks. Thus, 43 rabbits (21 in Group I, 22 in Group II) completed the 8-week course of treatment. Grading each side separately, 26 of 42 fusion masses (62%) in Group I and 24 of 44 fusion masses (55%) in Group II had radiographic evidence of fusion (p=.76). With gross palpation, 11 of 21 motion segments (52%) in Group I versus 13 of 22 motion segments (59%) in Group II were determined to have a solid fusion (p=.76). Histologically, Group I had a higher median score (6.0; range, 0 to 7 vs. 1.0; range, 0 to 7; p<.0001) and a higher fusion rate (76% vs. 45%; p=.004) than Group II.

CONCLUSIONS: Alendronate sodium appears to inhibit or delay bone fusion in a rabbit model. Presumably, this occurs as a result of uncoupling the balanced osteoclastic and osteoblastic activity inherent to bone healing. These findings suggest that a discontinuance of alendronate sodium postoperatively during the acute fusion period may be warranted.

PMID: 14749192 [PubMed - indexed for MEDLINE]

evidence is mounting I guess on these drugs. You know, Liza, that bone
necrosis occurs with them too? That is the dark underside that is coming to
light.
http://annonc.oxfordjournals.org/cgi...full/16/7/1207
http://www.cancerpage.com/news/article.asp?id=8122

I am worried that this may occur in non chemo patients at a slower rate, and
with time more will show up with negative results from these drugs!

--what might the dietary/supplement/exercise options be, to minimize bone loss and see if we can wake up some of the cells?

Can you put together a weight-bearing exercise program of any kind? What will your sinews/muscles tolerate? (Light weights/high reps?)

And (I'm sure Mrs. D will have suggestions here)--what kind of calcium/magnesium/Vitamin D3 regimen would optimize your bone condition?

BTW, I certainly empathize with your situation, and absolutely want you to avoid the kind of bone breakdown that Billye is suffering, but you're wrong about one thing. You also carry off these situations with grace. Maybe wry, sarcastic grace, but grace nonetheless.

delemma--danged if you do, danged if you don't take the adrenolates.
I too am/have been learning the 'hard way' about bone loss [far more than I ever could have imagined].
I fear that physicians are not as up to date on the newer cautions in the prescribing info as necessary. In my case I've been taking the adrenolates for over 10 years and a recent 're-read' of the info NOW includes the suggestion to take a 'break' at a 5-year mark. The info does not say for how long tho [I suspect 'THEY' don't know].
I am told and have read that other therapies are be available so there is hope. I will be finding out very soon tho, after more tests and a visit to the endocrinologist. I am sure that Billye is in that process of 'finding out' as well.
Every medication has the potential to help or hurt us. We usually find out after a precious price has been paid.
Liza Jane, I emphasize with your concerns and fears. Your concerns are far, far greater than mine. Below is a link on thyroid activity and how it can relate to other issues and conditions, particularly medications and supplements:
http://www.powerofprevention.com/thyroid/links.php
It seems that the whole endocrine system is linked to bone development and retention. The more I learn, I understand some, and am amazed by how complicated we humans are!
As I find out more, I'll post resouce sites.
For now have a couple of these: - j

I'm so glad you brought that up didn't know you have been on that.
All my Drs. and Bob's Spine Dr. believe it or agreed on something,
which is a miracle in itself, no Fosamax. Well all of them to many
serious side effects. Fosamax is very bad for people with certain
heart conditions. And not everybody knows they have the heart
problem. It was so odd to hear this from 4 different Drs. They all
reccomended high does of calcium,vitamin D and Magnisium also
a lot of green leafy vegetables.

The Spine Dr. said a lot of people see these ad's on TV and think or
lead to believe these are miracles. Yes they say the side effects at a
fast pace at the end. He really feels they can do damage.This does
bother me,1 don't thing i've ever heard 4 Drs. agree on the same thing.

You are a very brave lady,You do your homeword and in retun we benefit
from it. Thank you so much.. Sue

I have never been real enthused about the osteoporosis drugs out there. My family history of osteoporosis is very strong. My mother, who became very inactive, had a hysterctomy, refused HRT (prior to fosamax) lost about 6 inches in height. She now had pretty bad Alzheimers, so we dont really know how much pain she is in, but she denies it if we ask....on the other hand she doesn't know who we, her kids are.

You have to weight bear to prevent osteoporosis, and you need adequate intake of not just calcium, but vit. D and other minerals...It is good to take a balance.

Weight bearing can be as simple as walking a few miles even if painful, and lifing soup cans in the kitchen. A good clinical exercise specialist or physical therapist can help with exercises. They are essential. I know, that I at times have not followed thru as well as I should have, but something is better than nothing. Also, have your gait analyzed, in case you need orthotics...also that needs to be done every two years.

I stuck with an estrogen patch, very low dose, but that works OK for me, it isn't for every one....I have not had a bone density since my go around with IV steroids back in the fall of 2005, but I am not going back on them unless it is a matter of life or death. I dread having the bone density scan. I feel like I can't take any more bad news.

My gastroparesis will likely prevent me from taking any fosamax like drug as well.

Drugs are often dumped on the market too fast, especially if there is a market for them, and then other drugs which are potentially life savers for orphan diseases sit on the shelf because there isn't money to be made.

Men get osteoporosis too, but at a later age. Osteoporosis is more common in people who weigh less than 127# that sounds so specific...127!

This is one issue that speaks to pain control....if you don't have good pain control, you can not be active. I don't care if it takes morphine to keep some one upright and walking around, it is justified. When adequate pain meds are withheld and people become immobile, osteoporosis and pathological fractures occur, and this is devastating. I brought this up to my physician, and have had fairly good luck with pain control, although, I don't require morphine... yet. Without pain meds that work, whatever they may be for your specific case, discuss your immobility with the doctor, and make sure you get help, before disability increases.

I am wondering if there are any class action suits on the alendronates?

Knowing what to do is tough. We are all looking for breakthrus and ways to alleviate suffering, and sometimes, what gets recommended to us only contributes to suffering....It is a really hard road to travel.

Speaking of interventions to alleviate suffering....there are morphine pumps...I know they have a lot of downsides and contraindications, but some spinal patients have had good luck with them. It won't work for me, but maybe some of you could benefit, just be very very informed before you make any decisions. Consider all the downsides of spinal intrusion.

I just saw my feldenkrais person, and told her about the recommendations and my worries. She had referrals to people who specialize in bone "Bones for Life" a subgroup of practitioners with her training, and a machine the WBV which is supposed to stimulate bone growth.

But the most interesting comment she had was why get surgery like they suggest when I could just continue to wear a brace? If the brace works from the outside, why not use it for life?

This is a good thought. I'm going to stay with it for a bit.

I have often wondered about a brace myself. I bought a pretty expensive 'support' and you can melt this piece of plastic to conform to your spine...I just haven't gotten around to it....I didn't have a professional look at it though, and I am sure a PT might have some ideas.

I really should inquire about having a PT eval regarding something like that.

Great tip, thanks...It might really help. A brace might beat surgery for you, and gives me some hope that I can get some relief from my dessicated disc thingie too.

I'm trying to take a step back from Friday's doctor's appointment and my latest education from the web regarding fosamax. I feel I got myself too upset, and funny, it was one of those things where the more I learned the worse I felt.

So, I'm wearing a brace and it definitely helps the pain. Definitely. The person who fitted me in the surgical supply store said that the cloth braces with laces are better than the plastic molded ones because the molded ones tend to ride up, and the support is needed low down. It's pretty comfortable, just ugly. Plus, with only one prescribed and gotten, it gets ratty before I wash it, and it's looking a bit tattered. I think getting a couple more and dying them red or black would do me better!

Second, I spoke with another doctor today who said maybe somebody could just scrape the vertebrae up a bit again, like when it was initally done, and off fosamax, and maybe on Forteo (I'd have to check this out but they do seem to think that this one helps grow bone the correct way), I could fuse without having another major op.

I've an appointment with a bone specialist, but not until late June.

There's good evidence that vibration grows bone, and that exercise sets up vibrations which set up electrical fields, or something like that, that stimulates osteoblasts. So there seems to be a connection between why exercise helps and why the electric stimulator works. But also, doing exercises on a vibrating platform the VBV, seems to be the best for promoting bone health.

"Bones for Life" seems a good group.

I'm stressed out, and taking a step back.

My brace is cloth, with a pocket to add this plastic molded device if I want it, just over the low thoracic-lumbar region...the cloth support covers the whole thoracic and lumbar region. I bought the cloth support first, then later thought maybe I needed the plastic, but you are probably right...it probably feels pretty uncomfortable and could cause skin injury.

I do feel better when I use it, I just hate getting all fixed up in it...mine has velcro...it is super duper velcro and it doesn't move at all, but yours sounds like a better brace than mine. Mine wasn't cheap...I think over a hundred bucks, plus $35 for the molded plastic piece which I still have in its package...only problem is my brace has these shoulder harness pieces that after a while hurt my shoulders too...but it beats going without.