Category Archives: phosphonate

update: BISPHOSPHONATES AND MALIGNANT BONE PAIN: REBUTTAL AND COUNTER-REBUTTAL

 neil.burman@gmail.com

update 2 Oct 2010: a practitioner asks what to do for a  white female 58years:
1998 ductal cell. lumpectomy, radiation, 15 nodes removed.  Tamoxifen  5 yrs.
2009  lobular cell. double mastectomy, nodes removed.  Aromasin  for next 5 yrs.
Osteopenia -2.3  found inside  1 yr .    on
Boniva ibandronate  4 yrs, stopped recently. 
 Doesn’t want to take IV drug for osteoporosis. 24 hr urine calcium  normal.  High vitamin d levels.
takes a lot of calcium,  vit d, vit c, vit b complex sups. Takes Prilosec omeprazole for reflux and hiatal hernia. chronic insomnia.
The questioner does not reveal her bodymass index or resting morning cortisol level or insulin resistance- all of which may well be raised; nor give her crucial vitamin D and C  intake or vitamin D  blood level. It is a question of evidence, not opinion – dogma- or laboratory average population ranges , as to what are optimal intakes and blood levels.

This column  has regularly reviewed the conflicting views and evidence  on osteoporosis;  BNP and breast cancer; and the safe multisystemic efficacy of using the score of natural supplements- including appropriate combined hormone replacement therapy – that safely oppose both osteoporosis – bone and muscle frailty-  and the associated chronic major involutionary diseases of aging especially vascular disease, dementia  and cancer. .

 The antireflux proton pump inhibitors PPI drugs notoriously aggravate osteoporosis; and for average reflux are not necessary with use of slippery elm, apple cider vinegar, simple calmag  and sensible diet and lifestyle.  It has been known for years that PPIs  more than double risk of osteoporosis, so why take them?. 

On the other hand, the pluripotential hormones of darkness and light –  vitamin D3 and  Melatonin – combined with the other mulibeneficial natural supplements that synergistically relieve/ reduce insomnia,  reflux pain,  cancer, depression, memory loss  and all other significant major chronic degenerative diseases of aging.

As this column regularly updates, Metformin too is a natural supplement (plant) co-hormone- a veritable panacea-  that reduces all major chronic disease and mortality by about a third- including cancer; and  dementia perhaps via reducing serum amyloid levels.let alone tissue oxidation, glycation, vasculopathy. BPN has none of these extraosseous benefits, only deadly risks.  

 Similarly, appropriate transdermal human estrogen but not oral xenoestrogen- CEE-  reduces serum amyloid in postmenopausal women,  while low testosterone raises serum amyloid in men.

So middleaged patients are at terrible risk of anxiety depression hypercortisolemia, frailty fractures, vascular disease , cancer and dementia after cancer, especially with sex hormone suppression or blockade. They do not need the myriad risky designer drugs touted for prevention of more cancer etc, all they need urgently and permanently is the scores of appropriate natural balanced supplements as this column regularly reviews- most of which supplements can simply be mixed in a tub of customized powder blend to be drunk twice daily. .

:Feb 13, 2009    In response to  Death-knell-for-bisphosphonates-for-osteoporosis-breast-cancer-time-for-class-action-against-bisphosphonate-damage last week,  a world-renown emeritus professor of radio-oncology comments:

“the action of the bisphosponates BPN is to inhibit osteoclastic action and thus reduces bone resorption; the patients tell the story- they get immediate and sustained relief from bone pain; if they  are on opiates the need is much reduced. Of course palliative RT is valuable, but often if pain recurs after RT the BPN give welcome relief, at least in my experience.

The  IV BPNs are also very useful in the oft-times encountered hypercalcemia often threatening myeloma- and other cancer patients. I am not however, too conversant with D3 in this setting!” But the first reference links are the latest in the clinical field of BPN and cancer.

Other than  in terminal cancer cases- when it doesn’t matter what convenient pain relief is used-  the problem with bone pain in cancer always is, what is the cause? either bone resorption from the catabolic effect of cancer (via eg high parathyroid hormone PTH);  OR cancer eating away at bone itself, OR something else common OP  unrelated to the cancer.?

But FOR CANCER-RELATED bone pain lesions – whether directly from cancer there, or from remote metabolic effect –  where are the trials comparing BPN with other antiresorptive antineoplastic ANTIINFLAMMATORY ANALGESIC ANABOLICS ie testosterone (or occasionally estrogen/ other antiandrogen)  and vitamin D3?

Obviously bone metastases are attacked with appropriate chemo-/ xray XRT, cortisone, testosterone AND if deficient, vitamin D3.

To put it the other way round: where is the evidence that BPN – at cumulative cost and risk-  adds benefit to the multiple attack? where the evidence that- unlike testosterone and vitamin D3- BPN has any benefit except on bone pain? Hypotheses based on in vitro and animal and human cell culture studies have  not translated into even good observational comparative evidence favouring BPN as good benefit:cost ratio for osteoporosis or cancer.

The oncologist answers in the traditional mode, by experience that BPN works. But evidence-based medicine EBM asks where is the comparative evidence for BPN to challenge the evidence that we have better multi-attack without BPN – when these supplements are not equally commercially promoted and tested in controlled trials for the usual commercial  reason ?

The dream of drug manufacturers is eternal, that their raincheque designer drug- statin or BPN or antihypertensive- will prove to be a safe multisystem panacea as is metformin and many  other supplements like vitamin D3 or testosterone. But after more than 30 years of BPN and statins, no trial in humans has yet shown this for BPN or  statin or any other original designer drug.

BIG PHARMA-US GOVT CONSPIRACY FRAUD: THE NEVER-ENDING STORY OF DESIGNER SNAKEOILS- VIOXXES, FOSAMAXES, PSYCHOTROPES…

neil.burman@gmail.com  20100630

Pharma Fraud: the saga continues:

So Merck is also paying out $4,5billion to settle Vioxx damage cases…

  and now    Fri, Jun 25 2010  Jury orders Merck pay $8 million Fosamax damages 

 But as this column has described for almost 3 years  now, over 3000 cases of bisphosphonate osteonecrosis had already been  reported worldwide by 2006; the first case having been reported in about 1996.    

    And  leading university clinician Professor Dr  Scott Reuben gets a slap on the wrist 6 month jail sentence and > $300 000 fine for consistently faking drug  results ( Vioxx, Bextra, Effexor and even Lyrica ) for Merck and Pfizer- to bolster their multibillions sales. How much has he been paid / guaranteed to retire luxuriously remains untold.  

 So Meck now leads Pfizer ($3.4billion admitted  so far) in fines and damages penaties-  but both Pfizer    and Merck  still face untold billions in fines and damages in current ongoing litigation against them.  And worse to come- Merck and Bayer face massive damages claims over their contraceptives . This apart from the bakers’ dozen of shady practices listed against Bayer, of unquantified costs.    

  I recently saw my first associated case, a postmenopausal woman who had to have all her teeth removed and implants done after they came loose after a  few years on a bisphosphonate for osteoporosis prevention.  But perhaps my mother-in-law’s spontaneous cornflake collapse  of her lower femur in 1998 was my first case, someone had put her at about 70years  on bisphosphonate a few years before. She has never walked since, despite repeatedly failed  knee replacement. .

  There never has been the slightest  proven clinical justification for taking Vioxxes- Celebrex- Voltarens for pain, or bisphosphonates for osteoporosis/osteopenia, since there are safe  long-proven more effective natural painkillers, and safe supplements which restore normal bone without any risks, and (unlike bisphosphonates) with multisystem benefits that reduce all major common  degenerative diseases by 1/3 to 1/2 .   These modern synthetic designer drugs like bisphosphonates,   nonsteroidal anti-inflammatory “painkillers” ,  statins- cholesterolbusters, hypoglycemic drugs which actually promote obesity, neuro-drugs like  Neurontin, Lyrica, and Prozacs – Effexors, were and are  invented  to deceive patients into taking  lucrative $billion-dollar a year patent prescriptions  for widespread “prevention” and treatment, instead of the original natural supplements like eg herbs, biologicals, vitamins,and minerals which give relief and address the real causes with minimal risks and at low cost.        

 This  catastrophic fraud of Big Pharma- fostered by governments (for massive tax profits, job creation and ‘kickback’- God forbid that they are called bribes ) is  now exceeded in size only by the biggest Big Pharma scam ever,   last year’s  false swine flu pandemic scam  set up between the US government and Big Pharma, with multibillion dollar profits from unproven-value  mass testing,  vaccination and Tamiflu of unknown future disaster potential like thalidomide and stilbestrol proved to be.    (which in turn is exceeded perhaps by the biggest scam ever of modern times- the 2nd Iraqi war of GW Bush-Dick Cheney- Donald Rumsfeld- Halliburtons   that has now run most of this decade, the $Trillion War of Jo Stiglitz which will cost future generations of American and UK taxpayers infinitely more than that in compensation for injuries and deaths and debt; when there never were grounds – other than limitless oil to be pillaged- to invade Iraq any more than any of another dozen repressive dictatorship, when the obvious target against  Al Quaeda was always Afghanistan-Pakistan. )  

And the USA Govt and WHO (and hence most countries’ sheep -like regulators) actually changed the definition of a pandemic last year to perpetrate the trill$megabillion  swine flu  scam, and forswore proper randomized controlled clinical double-blind trials  to justify the vaccines and Tamiflu; and conveniently declared masses of old vaccine stores that were legally past their expiry date as recertified for use; and actually indemnified the vaccine manufacturers they chose against any future liability for failure of or complications from the vaccines.  

 Thus  the current USA government -with the backing of coerced allied governments  – invented the so far unproven if not risky swine flu vaccines, then handed the  recipes over to chosen manufacturers for free to produce and make $billions each within a year- with no liability –  at the incalculable expense of present and future taxpayers already reeling under the onslaught of USA-provoked overseas wars and  gigantic banking and oil cartel scams carefully orchestrated  by  deliberately failed  government   “regulation” which have caused the worst western global financial depression and environmental pollution  ever. .  

But these Big Pharma mafia  companies are bigger than the economies of many countries – apparently up to >8% of American gross domestic product- so they are protected by governments as too big to  jail or  close for fraud!   They couldnt care less about a few billion dollar fines  and damages for which they budgeted under cost of business- eg Bayer  last year paid $68billion for Wyeth the HRT  (Premarin- Provera) giant in North America…  

 As this column has previously reported,  the late greatest economist of modern times Ken Galbraith  would have said that  Big Pharma truly  rerpresents   the bared  backside  of western capitalist social democracy Naomi Klein’s  disaster capitalism (led by the modern pioneers of Human Rights for their own citizens if not their vassal dominions  – UK, Europe and USA)   – –  at its foulest .

IS IT ELECTROLYTE- OR VITAMIN- OR PROTEIN- OR FAT- OR STARCH- OR ACID- LOAD, THAT MATTERS? OF COURSE ALL DO.

neil.burman@gmail.com

Discussing the controversy about phosphate load in soda drinks,  Fenton’s Calgary University metaanalysis  discounts adverse effect of  soda-drink -based phosphate load and balance –  but  apparently does not dispute the acid-diet hypothesis of osteoporosis.

Their focus exclusively on calcium, phosphate and hydroxyproline  balance apparently studiously omits mention of hydrogen/bicarbonate/ pH/ other electrolyte  balance. The significance of calcium-phosphate intake and balance without correcting for pH and potassium-magnesium  balance is debatable. They found that “All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low .

The concept of pH and H+ balance has been established for at least  a century, so to avoid it in discussion of osteoporosis pathogenesis as Fenton ea do   is puzzling, considering especially that theirs  is a cost-free meta-analysis- not a trial or even an observational study. Thus their netanalysis  carries less weight compared to clinical studies like Wynn’s  EVANIBUSStudy.
Selye’s 1949 Textbook of Endocrinology mentions acidosis only in the context of  terminal diabetic or kidney failure – when clinical acidosis was obvious; but after the landmark first paper on Pubmed of Poul Astrup  in 1954 measuring blood acid-base balance (pH) in humans, Guyton’s 1961 Textbook of Physiology when we were students already detailed the crucial importance of pH maintenance by kidney and lung function- known  since the late 19th century from the work of Arrhenius, Henderson, Hasselbach, Beckman,  Sorensen ea ..

Wynn’s University of Lausanne EVANIBUSStudy published this month confirms that “There is growing evidence that consumption of a Western diet is a risk factor for osteoporosis through excess acid supply, while fruits and vegetables balance the excess acidity, mostly by providing K-rich bicarbonate-rich foods”.

so if people wont reduce their high meat intake (which damages bones brain and heart as well as kidneys),
– quite apart from discouraging commercial unhealthy ‘sodas’ and “fruit juice” due to adverse sugar, phosphate and aspartame intake –
at least we  can and must  protect people  against all major chronic degenerative diseases, we must reduce all-cause mortality by encouraging a potassium -magnesium (calcium) -zinc-boron  -high vits  (especially D+K+B+C) and fish oil  supplement . . especially in eg Asians who take a phosphate-rich (eg chapati) diet.

Naturally the FDA – (read  Food and Drug Antihealth Agency)  industry mafia for whom Only Disease Pays- are determined to suppress such evidence-based prevention and supplements  so as to maximize their profits from  the nefarious processed drink and food chain (soda drinks) and designer drug industry interests (eg bisphosphonates – which may reduce osteoporotic  fractures by half but have major adverse effects and do nothing to reduce the global burden of degenerative -frailty-  diseases and thus non-fracture mortality) .

It will be interesting to see what food and drug companies support Fenton’s Calgary Alberta   impeccable nutritional study  that denies adverse effect of soda-drink phosphate loading.  Their paper does not specifically state where the concept of the study originated, and that there was no indirect  support or input from the food and drug industry for the University or for  their study.

Just another year of Health Censorship, Government-Big Pharma criminality.

hats off to Mike Adams the Health Ranger for a run-down on 2009 – a record  year of USA-government  led health censorship and Big Pharma crimes in many countries notably also  UK and Europe. But national authorities who played the pandemic and vaccine and Tamiflu  cards without evidence  remain silent  as the farce is exposed.

Sweden actually banned media reporting of vaccine-associated deaths  and miscarriages at a time when vaccine-associated deaths -5- exceeded those even vaguely attributable to the swine flu – despite the fact that GSK soon had to withdraw hundreds of thousands of the same vaccine in Canada due to similar serious reactions. And politicians may try to legislate blanket indemnity for themselves and their paymasters in Big Pharma, but no independent higher court will support this when it blows up in their faces- Big Pharma, and the politicians/administrators/”experts” responsible, will be held personally liable for damages for their criminal deliberate breach of common sense about requiring proper clinical trials before releasing such unsubstantiated rubbish. Group conspiracy is no defense.

Apart from the numerous issues Adams focusses on in his NaturalNews column,

this HealthSpanLife column has  this year spotlighted the dangerous Big Pharma overpromotion for profit and ill-health of the biggest- and risky-  modern and mostly unnecessary money-spinners for chronic disease apart from vaccines:

oral antidiabetics;  strontium ranelate and bisphosphonates against osteoporosis; 

psychotropes;

antihypertensives; antidementia,

antilipidemia,

antithrombotic and

anti-imflammatory drugs ;

and black cohosh.

By year’s end, no evidence has been produced to refute our conbined accusations of conspiracy fraud against the US Government- the FDA- and global Big Pharma for disease-mongering  and promotion of unproven new drugs at all cost for profiteering.

The irony is that as AIDS denialism has passed in South Africa with the demise of  the  infamous Mbeki-Manto-Zuma  delusions, the local population   is being decimated by the apocolyptic  plagues of the ANC Mbeki-Zuma era – violence, poverty,  demolition of state school and nursing  education and the SA Police and Justice Departments,   joblessness, civil service and corporate corruption,  starvation, obesity, alcoholism, smoking, hard drugs, AIDS, tuberculosis and cholera. At least AIDS sufferers begin  to see the roll-out of antiretrovirals. These – a giant profit for Big Pharma-  have turned AIDS from a 7-year death sentence to a lifelong manageable  degenerative disease like diabetes.

Another irony is that Zimbabwe flourished for the first 20 years from 1980  under under the highly educated teacher Mugabe’s  brutal genocidal rule- he massacred his political opposition, but left alone  the good education, health and food (white-led farms employing and feeding millions)  that he inherited. Then from the year 2000- when he saw how the ANC’s  national sabotage was being ignored by the world  as the Nbeki-Zuma- Manuel-Asmal  leadership  ignored the constitution and immediately – from the mid- 90s- set abo systenatically  pillaging – selling off-  national assetts to enrich their buddies and make the poor poorer, with destruction of the education, health, nursing, home affairs, energy, forrestry. army and police services- Mugabe’s gang realized they could do the same- and in so doing, turned Zimbabwe from an educated land of plenty and food exports to a terrorized basketcase from which probably half the sizicens have fled as refugees- fled from ongoing government brutality starvation and plagues. Throughout this time- while formerly Mugage had housed and financed the ANC to fight the war against South African apartheid- the Mbeki-Zuma government has till this day done nothing but support Mugabe and his jackbooted brutal regime – despite his destroying the Zimbabwe economy and food supply- with praise and massive taxpayers’ handouts.

And this as the vaccine-autism  link ( Andrew Wakefield trial) at the GMC grinds to it’s 7th year and apparent verdict  next week. Irony indeed as the scandal over the US govt -big pharma coverup on fraudulent if not dangerous  flu vaccines and antiflu drugs the past 35 years comes to a head. It is over 2 months since we personally asked the local Roche representative to supply clinical trial evidence to justify Tamiflu- naturally they have not supplied any because there is none. The same goes for the “swine flu vaccines”.  And the  cervix cancer vaccines.

 
 

//

WARNING re HEAVY DAMAGES FOR NEGLIGENT PRESCRIBING: BISPHOSPHONATES – FOSSY DRUGS- FOR OSTEOPOROSIS?

This column last considered bisphosphonates BPN in February. This  reviews some new papers published since.

ADVANCED  CANCER with bone spread:  Recent major (Cochrane)  reviews confirm that BPNs may be  valuable in   advanced prostate and  breast cancer ,  for reducing skeletal events and maybe pain, although they   do not clearly  influence disease progression or patient survival.

OSTEOPOROSIS: It is now almost 5 years since the balloon went up on the unnecessary major risks of BPN for osteoporosis.  So anyone who was prescribed these dangerous drugs since then for osteoporosis, without the rare special  indications, and who develops BNP-related complications  (or osteoporosis-related fractures) has a strong case for heavy damages against the prescriber, the dispensing pharmacy  and regulator eg the State clinic or medical plan who/which advised/ allowed use of the drug for that condition. .

Bisphosphonates were invented over a century ago but developed over the last 40years  for clinical treatment of metabolic bone diseases,  with the first human trials reported about 35 years ago (Heaney 1976). Why have they been exhaustively tested and now routinely used for prevention and treatment of aging osteoporosis, despite their considerable cost especially risks, and lack of global benefit?

Obviously because as patented designer drugs they are profitable to the Disease Industry – despite the fact that their biggest section on Wiki is about their rare but major adverse effects- to quote Wiki :

  • Oral BPN can cause upset stomach, inflammation and erosions of the esophagus,
  • Intravenous BPN can give fever and flu-like symptoms after the first infusion. The  slightly increased risk for electrolyte disturbances is not enough to warrant regular monitoring.
  • BPN have been associated with osteonecrosis of the jaw – the mandible twice as frequently affected as the maxilla- and most cases occurring following high-dose intravenous administration  for cancer patients. Some 60% of cases are preceded by a dental surgical procedure (that involve the bone).
  • severe bone, joint, or musculoskeletal pain has been reported.
  • BPN  use ( zoledronate and alendronate) is  a risk factor for atrial fibrillation in women. The inflammatory response to BPN or fluctuations in calcium blood levels have been suggested as possible mechanisms..
  • Matrix metalloproteinase 2 may be a candidate gene for BPN-associated ONJ since it is the only gene known to be associated with bone abnormalities and atrial fibrillation, both of which are side effects of BPN.
  • Long-term BPN  use resulting in severe or over suppression of bone turnover especially at the  femur sub-trochanteric region.  Micro-cracks in the bone maybe  unable to heal and eventually unite and propagate, resulting in atypical fractures, which  tend to heal poorly and often require some form of bone stimulation eg bone grafting.

NO COMPELLING INDICATIONS FOR BPN IN OSTEOPOROSIS: the Wiki entries for BPN  and osteoporosis are cleverly written by BPN promoters / marketeers – they fails to justify  why BPNs are “the most popular first-line drug”… and the overwhelming evidence that favours combined natural supplements: eg that in the Womens Health Initiative, appropriate hormone replacement HRT ie started soon after menopause is safe up to 10 years of use, halved fracture rate and colon cancer, and lowered all other chronic major degenerative diseases AND breast cancer AND  premature deaths by a third.  BPNs have risks but no  benefits other than fracture reduction- ie for osteoporosis, no compelling indications  and the legal eagles are hungry.. .

BPN-ASSOCIATED OSTEONECROSIS IN LONG BONES: Guanabens from Spain first described long bone fractures related to BPN in 1994,  and more such cases (iatrogenic Toulouse-Lautrec disease) are reported now from the UK.

ATRIAL FIBRILLATION:   Denmark reports some 30% increase in potentially crippling atrial fibrillation in patients with fractures treated with BPN  – whereas it is common cause that appropriate supplements drastically reduce arrhythmia eg fish oil halves sudden death.

Italy now reports increase in hypocalcemia and raised serum creatinine ie kidney impairment after BPN  for cancer . . Sweden reports no benefit of 2 years’ BPN   on knee prosthesis migration. The incidence of metabolic bone disease and all other system complications in intensive care is notorious – and a   Princeton report gives no justification for BPN use in ICU when all the safe natural supplements are essential and ensure better protection globally..

Canadian study shows that ” managed intervention” after osteoporotic hip fracture prevented  4 new hip fractures and gained 4 quality life-years –   but the available abstract omits what the interventions were, and whether survival was increased.

And while all rational evidence-based appropriate prevention and treatment of osteoporosis – the permanent baker’s dozen of safe natural supplements- reduce all-cause chronic degenerative disease and mortality by at least a third, without any risks, – BPNs  have increasingly recorded risks both short term and long term, with no extraskeletal benefits, despite reducing the fracture risk (spine -Cummings 2002; hip Nguyen 2006) by up to a half.

OSTEONECROSIS OF THE JAW ONJ:   first reported in 2003,   only 26 cases of ONJ  on oral BPN could be found  reported worldwide up to Sept 2006  in a  2007 University Pennsylvania study . Only  15 % were men, and the majority involved the mandible.    Now Israel alone reports another 100 cases of BNP- related jaw osteonecrosis – fossy jaw  – and 16% were on oral BPN. The incidence of OJN is  speculated to be between 5% and 11% in cancer patients treated with BPN.

A world-wide  panel produced the  2008  Canadian Consensus Practice Guidelines for BNP Associated Osteonecrosis of the Jaw, but did not estimate  the incidence of ONJ.   It concludes  that “High-dose intravenous BNP have been identified as a risk factor for ONJ in the oncology patient population. Low-dose BNP use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ”  “BPNs have become a cornerstone in the management of skeletal complications of malignancy as well as osteoporosis and metabolic bone disease, as these agents offer tremendous benefit to those with malignancy or metabolic bone diseaseDue to limited and misleading public information regarding ONJ, many patients have discontinued  BPN treatment, resulting in inadequate care of the underlying skeletal condition.”

But the Canadian Consensus paper fails to clarify in what way BPN offers “tremendous benefit” to those with osteoporosis? The  consensus of the majority of practitioners who do not recommend BPN for osteoporosis is that evidence still shows that appropriate HRT with other standard supplements is  the best prevention and treatment not just of osteoporosis but of all the common major degenerative diseases of aging. (The International Menopause Society). This eternal truth and aim- the wellbeing of seniors- is the imperative, not the wishful thinking of Big Pharma to replace natural supplements with designer magic bullets for each disease.

By far the most comprehensive and objective review is  the American Association of Oral and Maxillofacial Surgeons   Position Paper January 2009 Update on Bisphosphonate-Related Osteonecrosis of the Jaw BRONJ: Indications and benefits of BPN therapy:

Intravenous (IV) BPN are primarily used and effective in treatment and management of cancer-related conditions including hypercalcemia of malignancy, bone metastases such as breast, prostate and lung cancer, and multiple myeloma- for which the clinical efficacy of IV BPN  is well established.

BPN have not been shown to improve cancer-specific survival, but they have had a significant positive effect on the quality of life for patients with advanced cancer involving the skeleton.

Oral BPN: By far the most prevalent and common indication is osteoporosis and  osteopenia. They are also used for a variety of less common conditions such as Paget’s disease of bone, and osteogenesis imperfecta of childhood.

INCIDENCE OF BRONJ: Based on case series, case-controlled and cohort studies, estimates of the cumulative incidence of BRONJ range from 0.8%-12%.

ORAL  BPN BRONJ: Surveillance data from Australia estimated the incidence of BRONJ for patients treated weekly with alendronate as 0.01-0.04%. In a survey study of over 13, 000 Kaiser-Permanente members, the prevalence of BRONJ in patients receiving long-term oral BPN therapy was reported at 0.06% (1:1,700).

Demographic and systemic factors:  In the original Position Paper, age, race, and cancer diagnosis with or without osteoporosis were reported as risk factors for BRONJ. Seven studies report increasing age as consistently associated with BRONJ. Sex was not statistically associated with BRONJ.  Other systemic factors or conditions, i.e., renal dialysis, low hemoglobin, obesity, and diabetes, were variably reported to increase the risk for BRONJ. Malignancy type was not statistically associated with an increased risk for BRONJ.

Genetic factors: Sarasquete et al, demonstrated that genetic perturbations, i.e. single nucleotide polymorphisms (SNPs), in the cytochrome P450-2C gene (CYP2C8) gene were associated with an increased risk for BRONJ among multiple myeloma patients treated with IV BPN.

Preventative factors  The AAOMS Taskforce on BRONJ recommended that patients undergo dental evaluations and receive necessary treatment prior to initiating IV BPN therapy.  In addition, given the long-term biologic activity of IV BPN one may hypothesize that different dosing regimens may be equally effective and decrease the risk for BRONJ.

Using a retrospective cohort study design, Coso et al, evaluated the BRONJ and skeletal-related events  e.g. pathologic fracture in multiple myeloma patients using different dosing schedules for zoledronate. These findings suggest that alternative dosing schedules that reduce IV BPN exposure have comparable outcomes in terms of preventing SREs and a decreased risk of BRONJ.

The effectiveness of hyperbaric oxygen therapy as an adjunct to non-surgical and surgical treatment is under investigation at two institutions where a randomized controlled trial is underway. Preliminary results have shown some improvement in wound healing and long-term pain scores, but its use as the sole treatment modality for BRONJ cannot be supported at this time.

Yet despite the fact that osteoporosis and fractures are closely related to and occur along with the major causes of aging disability and premature death – 20% of osteoporotic hip fracture victims die within a year- BPNs have not been shown to reduce any let alone all the other aging diseases let alone premature deaths. The closest a study came to assess the issue was a Singapore analysis of the  30year old clodronate used for up to 2-3 years after breast cancer  – which drug showed no influence on overall survival.

This failure of global benefit of BPNs – which are  in fact never indicated except rarely eg as palliation in preterminal cancer bone lesions – raises the question of criminal negligence when doctors prescribe and medical schemes and Regulators allow BPN use for osteoporosis. Why are BPNs allowed and prescribed when they have no global benefit but numerous serious risks; and when conventional lowcost natural supplements combined do nothing but global good.   eg essential fish oil, essential vigorous-dose blend of vitamins-minerals-biologicals-herbs, essential appropriate HRT , and essential galega-metformin in the overweight let alone obese each lower all-cause chronic morbidity  and death by a third to a half.

It is no defence that adverse effects are rare when  they are  sometimes deadly, and never worth the risk of these drugs since there is rarely overwhelming need to prescribe such drugs- for which there are safe  natural and far more effective alternatives.

CASE REPORTS: In 2007 we saw a well-built  physically active woman of 61years, whose bone density had fallen some 9% on regular DEXA screening  since menopause despite the usual calcium-vitamin D supplement. In 2008  she  decided to delay HRT because of  strong family history of breast cancer. A year later at followup DEXA  on just fish oil plus a modest dose of the standard HealthSpan For-Bone  supplement blend (calmag zinc boron manganese; proline; and vits B6-9-12 – C- D3 & K2), her DXA BMD has risen 2% (2.5% at the spine, 1.5% at the hip).

A small slim 61year old bookkeeper presented a year ago on just calcium &  vitamin D, her 2007 DEXA spinal density 0.99 having fallen 1% from  2005 ie T -1.6  but her hip down 6.3% from 0.792 to 0.764 ie T-2.  Since then, on the Bone Blend and a little estrogen-progesterone-testosterone cream daily, her spine has stayed constant but her hip BMD has risen 2.4% to 0.783.

A new review from Toulouse France has the last word: “Postmenopausal osteoporosis is a chronic disease which justifies long-term treatment.  Efficacious available modern  fracture-reducing drugs raise the question of the best treatment strategy in postmenopausal women .    In this regard, HRT, which allows a more global approach to the menopause-induced consequences of hormone deficiency than the sole prevention of osteoporosis,  should be privileged… Use of BPN or strontium ranelate should be thus (at best) be reserved for a more advanced age, when the prevention of hip fracture becomes mandatory“. .

Yet, because it is profitable, the fashion grows to treat the elderly with grossly expensive designer oral strontium, or designer injections of BNP or hormone analogues (of calcitonin or parathormone) – despite the fact that these experimental agents have no extra-skeletal benefits (ie improving cardiovascular, muscle, immune, brain function),  have never been tested in longterm studies  for at least 6-10 years to test their safety as has eg HRT in the Nurses’ and WHI studies.

But millions of years of bipedal evolution, and numerous studies over the past century, show that all that is required to  maintain maximum mobility, mind and mood to enjoy life is lifelong supplements as listed above, appropriate to youth, parents, the middle-aged and seniors.. including healthy seniors’ sexuality. It is  too late postponing  prevention  till wished-for healthy advanced age- which most do not reach due to early demise, or irreversible crippledom from largely avoidable fractures, strokes, heart failure, arthritis, or dementia.

The Israelis’ maxillofacial team lament that “Solutions for decreasing morbidity and poor outcome of ONJ remain elusive.” The answer is painfully obvious: avoid iatrogenic ONJ by avoiding  BPN -even orally- except for advanced cancer with bone metastases, but back up lower dose  BPN  with all the  anabolic supplements.

A risk of “only” 7 in 10 000 may reassure a patient being offered BPN for  osteoporosis- but if she decides to sue for damages for prescription of totally unnecessary hazardous therapy, the prescriber doesnt have a leg to stand on when the gold standard is appropriate titrated supplements (including HRT)  without risks since  they reduce all risk by at least one-third.

As  wise Chinese taught 2600 years ago, Society, Authorities, Regulators, health professionals have a sacred obligation to above all else prevent avoidable premature death and crippledom with the freely available and low-cost well-proven natural supplements. These must prevail despite the best efforts of Big Business, Big Pharma and their academic and political lobbyists (Governments, Regulators) worldwide to ignore if not outright suppress safe effective old natural  supplements  (as the FDA and EU are doing) in favour of Diseases and Modern Drugs that Pay – but do not reduce all-cause  disease and mortality .

ndb

TOWARDS MANAGED AGING part 3

The first two chapters have covered musculskeletal, cancer and cardiovascular diseases and HRT.

THE COMMON PATHOPHYSIOLOGIES:  So apart from genetic programming, there are at least six possible pathophysiologies common to the preventable aging co-morbidities of apoptosis (our predestined cell death- only cancer cells are immortal) , fattening-diabetes-cancer; osteoporosis-fractures, and CVD-stroke.

What ranking to give them depends on the individual and tribe.

*catabolism by (relative) gonadopause ie sexhormone deficiency without a balancing fall in catabolic cortisol levels- especially when gonadopause is brought on early by sterilization, hysterectomy, infection, cancer therapy, other chronic disease, or high stress and pollution;

*nitric oxide depletion;

*lifelong and progressive deficiency of the score other human biologicals- especially the marine essential fatty acids (EPA eicosapentanoic acid and DHA docosahexanoic acid- so essential from conception to death for both cell maintenance and immunity;

*increased reactive oxygen species ROS due to falling endogenous and dietary antioxidants;

*common aging-related deficiency of  minerals eg magnesium, calcium, zinc, chromium, lithium, selenium, manganese, boron,  (iron); vitamins; and human biologicals eg chondroglucosamine, CoQ10, carnitine, ribose, arginine, carnosine, Nacetylcysteine (and the sex hormones);

*insulin resistance – prediabetes, metabolic syndrome, PCOS, diabetes; and

*accumulating overload of: multiple metals eg cadmium, iron, aluminium, mercury, lead, arsenic, asbestos, copper (even zinc and iron); radiation; and estrogenics eg pesticides, plastics and sexhormone tablets, and from smoking, food and environmental pollution, that can simultaneously promote cancer, neuro-/vascular and osteoporosis problems.

There is a huge basket of natural supplements- fish oil, cal-mag zinc, boron, lithium, the vitamins A (bcarotene) to K, and the human biologicals (eg proline, CoQ10, arginine, ribose, carnitine and appropriate hormone balance with eg testosterone-estradiol -progesterone, growth hormone), and galega and other herb extract. These are trophic in improving anabolism ie immune protection, tissue regrowth, antioxidation, optimal NO levels, and preventing sugar tissue damage- advanced glycation end products AGES, atheroma and arteriosclerosis as well as collagen and mineral loss from diverse muscle and bone – ie preventing many of the risk factors for both fractures (frailty, weak bones and muscles – skeletal and smooth ie gastrointestinal and heart ) and vascular and immune and malignant disease .

Given the common pathogenic factors of all the common major aging diseases, one should simply add the natural supplements- arginine glutamine and proline, vitamins, minerals, glucosamine-chondroitin, and the other natural insulin sensitizers eg N acetyl cysteine, ribose, carnitine, CoQ10 and galega officinalis, to combat all aging diseases; and when hypogonadism becomes likely- with chronic illness, or from middle age- add appropriate parenteral balanced physiological-dose testosterone-estradiol- progesterone to restore the average levels of healthy slim youthful adults.

Detox: While some of these above supplements may be chelators – removers of heavy metals- in their own right, the high prevalence of metal overload may justify routine addition to supplements (within recognized tolerance and safe limits) of extra harmless non-prescription chelators like, vitamin C, thiamine, magnesium, selenium, zinc, garlic, lipoic acid, malic acid, and bromelain, and the aminoacids eg calcium EDTA, carnitine, cysteine.

CONCLUSION:

with plenty of research to prove it, it is never too early, and never too late, to  do easily what’s necessary to avoid most of the risks for the linked aging diseases that disable and kill prematurely – frailty, obesity-diabetes, circulatory (heart, stroke), arthritic, fracturing, blinding, deafening, dementing and early death.

What’s necessary is simply

*sensible diet and lifestyle including exercise and recreation;

*lifelong appropriate vigorous nutritional supplements including appropriate hormone replacement; and

*avoidance of smoking and overweight, sugar and cooked fats, and if possible avoidance of any modern man-invented drugs (or foodstuffs eg aspartamate, cornstarch) for chronic use including hormone therapy- especially man-designed hormones, and drugs invented to replace natural drugs eg to reduce cholesterol, obesity, fractures, pain, anxiety, depression, hypertension, memory loss etc.

Usually both natural supplements and other complementary therapies, and old proven “drugs” (like metformin for overweight/ infertility/ diabetes, or lowdose reserpine + lowdose co-amilothiazide as baseline therapy for all hypertension) are both safer and better- if not as fast- as modern marketed therapies.

(for detailed scientific links and refs, see the technical version of 13 Sept 2008)

DEBUNKING THE MYTH OF BISPHOSPHONATES: time for class action:

Again we must ask: why are patients with cancer, let alone those with  “simply” osteoporosis,  given bisphosphonates?

Body’s review from Belgium in 2006 sums  up the belief system created by the Disease industry: – cancer patients are given it for osteoporosis, or for metastatic bone disease with high blood calcium.

Yet a new paper from Gutenberg University Germany (Al-Nawas ea)  shows that 1 in 20 ie 5% of 75 women with breast cancer  given bisphosphonate between 2000 and 2006 developed osteonecrosis of the jaw. That’s just the severe cases identified.

The far bigger study from St Louis & Arkansas Universities  last year (Wang-Gillam ea)  surely gives the  answer for most cases: why give toxic bisphosphonates which do not address the underlying pathogenesis- when this is always multifactorial.  They showed that, as in osteoporosis without cancer, most such patients have simple easily correctable deficiency of vitamin D let alone many other universally deficient supplements. They found that “of 321 women with breast cancer given bisphosphonate,   267 were taking the drug for osteoporosis and 54 were taking the drug for metastatic bone disease. Of the 209 who had had a vitamin D level checked, only 3.8% received more than 600iu vitamin D a day. Only 38.8% patients had a 25-OHD level >30 ng/ml; Serum PTH levels rose as serum 25-OHD concentrations declined to <30 ng/ml. Even in the group of patients with a serum 25-OHD level >30 ng/ml, four of 74 (5.4%) had secondary hyperparathyroidism.”

“This study revealed that vitamin D insufficiency has a high prevalence among breast cancer patients being treated with a bisphosphonate for osteoporosis or metastatic bone disease and that supplementation of calcium and vitamin D is underused in the care of these patients. This finding suggests that it is probably more appropriate to set the level for vitamin D adequacy to a screening 25-OHD level of >30 ng/ml ie >105nmol/L. we advocate routine screening of the 25-OHD concentration for vitamin D deficiency in general.”

Now Cohen ea from Columbia University New York question  the use of bisphosphonate in younger women with osteoporosis, when easily correctable deficiencies are so often the cause.

And a new  Kaiser Permanente community Effectiveness study  by Feinstein ea in fact shows that in 10 years to 2006, on bisphosphonates some 1830 elderly women at high risk of osteoporosis fracture had no significant reduction in major fractures.

We know that bisphosphonates require adequate vitamin D levels to work. The bizarre joke is that Big Pharma is even marketing bisphosphonate paired with lowdose vitamin D. Why on earth poison harmless effective vitamin D with a toxin that can cause bone collapse, gullet ulceration and obstruction, toxoderma, muscle damage and arrhythmia?

We know that even oral HT with CEE and progestin reduces hip fractures by up to 40%; but we also see regularly that combined HRT including parenteral testosterone and all the other proven supplements  steadily increases bone density into the normal range in the severest  osteoporotic, AND reduces  especially falls and fractures by reversing frailty.

As Brown   says in a comprehensive 2008 review, restoring vitamin D deficiency with 800 instead of 400iu daily already doubles the reduction in fractures, and greatly reduces falls in the elderly. Hence we must agree with her, and Geller and Adams from UCLA 2008, that vitamin D in effective dose – reportedly to a safe  meaningful blood level of >35ng/ml ie 100-130nmol/L, in company with appropriate parenteral combined HRT and  the other dozen balanced vitamins and minerals,  can more than halve  both fractures and all other common degenerative disease risks. We have discussed repeatedly in this column that appropriate  testosterone- estradiol replacement greatly reduces all-cause morbidity and mortality even in men or women after cancer.

So the question remains: why (except for marketeering, profit motivations) are patients with osteoporosis or cancer metastases being given notoriously toxic bisphosphonates- which have never been shown to be safe let alone beneficial long term – when it has been known for decades that adequate replacement with natural appropriate supplements- including balanced calcium, magnesium, zinc, boron, manganese; vitamins B,C,D & K, and appropriate physiological testosterone and estradiol to restore the healthy balance of  healthy youth- and especially vigorous vitamin D3 supplement. 1, 2 – rebuilds and maintains musculoskeletal health..

Osteoporosis is like diabetes, hypertension, obesity, cancer, cardio/neurovascullar, arthritic, mood and dementing diseases, a multi- $billion-dollar a year  target for the designer drug industry -let alone the diagnostics and invasive medical  industries. For these industries, lucrative drugs, tests and surgery far outweigh the boring counseling about lifestyle and lowcost micronutrient preventatives- which would make designer drugs, costly tests and surgeries – hospitalization-  virtually obsolete for medical conditions except for those who live to be the oldest of the old.

The NIH years ago introduced incentives in far higher consultation fees  for cardiologists and cardiac surgeons to spend time counseling patients about better diet, lifestyle and medicine use instead of invasive procedures and surgery- which do not address the underlying pathogenesis eg overweight, stress-cortisol, insulin resistance. Such an approach resulted  in eg cardiologists Drs Siinatra and Roberts virtually abandoning invasive cardiology since virtually every patient with ischemic heart disease could and can  be cured with intensive consulting room management including optimization of designer drugs and curative supplements.

It is apparent that no mainstream physicians bother to publicize this approach to the equally common but far more disabling problem of osteoporotic fractures- which kills or leaves impaired far more patients than vascular disease. eg the  the latest reviews of treatments for postmenopausal osteoporosis  available as abstract or fulltext on Pubmed- a  Canadian consensus 2003 , Hauselmann & Rizzoli 2003 and Cosman 2005 failed to even mention true preventatives beyond futile lone calcium and lowdose vitamin D – despite there  being study evidence to support vitamins B6-9-12, C,  K,  magnesium, zinc, boron, manganese,  (fluoride if low in local water), and physiological replacement of deficient testosterone/ DHEA -estradiol.

No-one is going to support trials of  combined natural supplements to prevent and treat osteoporosis when the disease industry, as well as the osteoporosis associations which they invariably fund and feed with drug information, all have vested interests in avoiding simple universal combination prevention.

The study from Wang-Gillam et al opens the way for wider class actions 3, 4 by Regulators and  patients against the promoters,  marketeers and prescribers of all bisphosphonates, since it has always been clear that  adequate replacement of natural supplements would have done  and do far better.  But Regulators are in fact co-conspirators since they allow modern drugs to be widely used without evidence that they are as good as long-used safe and cheap  old supplements.

Despite the high cost (in money and suffering) of bisphosphonates and other designer drugs eg Forteo against osteoporosis, no trials have shown that they reduce all-cause mortality – ie unlike natural supplements (which address all common diseases – improving defenses against fractures, depression, infection, cancers, vascular disease, dementia etc, and thus halve premature morbidity and mortality),  bisphosphonates’  only action is to -disastrously  –  stop necessary bone remodeling. It is common cause that  the chief causes of osteoporosis- muscle and general frailty, aging’s catabolic dominance- are not aided by designer drugs like bisphosphonates and Forteo; only anabolic agents like parenteral testosterone replacement, vigorous vitamin D and the combination of other micronutrients listed above do so.

Avoidance of this central issue – failure to address underlying pathogenesis and numerous simply correctable micronutritional deficiencies  –  is the major fraud of teaching, marketing and promoting predominantly designer drugs and technology – in which fraud Regulators, politicians and often academics cravenly conspire, Elaine Feuer’s The FDA  War against Humanity.  Not for nothing did one of the greatest social philosophers of the 20th century  Ivan Illich call organized medicine- the capitalist  Disease Industry –  Medical Nemesis.

Is it an overstatement to say that bisphosphonates are clearly even worse chronic disaster than statins – where the damage is usually insidious but reversible- or NSAID class drugs- which can simply kill by thrombosis or bleeding; or SSRIs-  which can trigger suicide? The other modern drugs (after thalidomide)  do not, like bisphosphonates, disfigure and maim.