Monthly Archives: July 2009

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

SPOTLIGHT YET AGAIN ON UNNECESSARY LEGALIZED KILLER ACETAMINOPHEN/ PARACETAMOL

Isn’t it pathetic that we  should  still have to be worrying about such avoidable toxicity and deaths as reported again  (the Wall Street Journal – The Unsafe Side of Acetaminophen) from unregulated purchase of the unnecessary synthetic designer drug panado/Tylenol/Acetaminophen/paracetamol/docdol?

when there is virtually nothing that can be safely consumed in more than moderation, when Regulators continue to allow vendors to sell and consumers to freely buy & consume alcohol, aspartame, sugar, cigarettes , and excess salt, cornstarch, cooked fats when these are lethal even in little more than tiny portions?

and even more tragic when addition of a small amount of lowcost natural supplements would make paracetamol vastly safer- eg vitamin B6, N-acetyl cysteine +- milk thistle/ stinging nettle;

and when paracetamol is unnecessary, when for mild-moderate pain, a simple safe mixture of eg some physical therapy eg exercise, stretching, massage or pressure; and/or natural supplements do as well (eg vitamin C, MSM, curcumin, bromelain, feverfew-buffered by some calmag) for brief pain; plus appropriate eg fish oil, vitamin C & chondroglucosamine for chronic pain.

Even educated working people choose to be ignorant, dangerously careless about the risks of what they consume. So crippling disease and deaths from the unnecessary (except salt and cooked fat) toxins discussed above is caused by those who allow and sell such toxins.

It is long common knowledge that even 6 paracetamol (3000mg) consumed at once can be fatal through liver failure. So it is incomprehensiible that regulators till now allow up to 4000mg a day to be taken especially without safe cheap antidotes.

Given that man is the most violent, destructive thinking creature on the planet, at least guns have a redeeming purpose as a chosen method of defense, survival. This argument cannot be made for cynically commercially sold paracetamol, sugar, cornstarch, alcohol, cigarettes and cooked fats – let alone NSAIDS nonsteroidal antiinflammatories including Cox2 blockers eg Vioxx, celebrex as painkillers.

As usual, the FDA (and the Regulators worldwide that blindly follow it)  remains as criminally negligent as ever- The FDA’s War Against Humanity –  in allowing patients to be killed by protecting Big Pharma that markets barely tested new largely unnecessary synthetic drugs as well as unrestricted sales of eg sugar, cornstarch, alcohol, aspartame, NSAIDs and acetaminophen.

RESTRAINING UNNECESSARY RISING COSTS OF COMMON DRUG THERAPY AND CONFLICTS OF INTEREST:

The review published yesterday by Discovery Health  “Medicine expenditure up by 26% in private healthcare industry” based on the Mediscor Medicines Review resonates with this week’s editorial from JAMA on Resolving Unreported Conflicts of Interest. Apart from anticancer therapy (which affects relatively few patients but is very costly), by far the two top drug costs to the private  health system in RSA  are antihypertensive and hypolipidemic drugs.

But why are these two groups of drugs 1/6th of  local private medicines expenditure?

The reason is quite plainly vested interests- between prescribers, drug developers and retailers, for  well-known reasons:
1.  Modern western medicine  rarely attempts to address the pathogenesis  of disease – it takes too much effort by prescribers and patients to try to change diet and  lifestyle. And  the only “modern” drug that addresses the main causes of the common degenerative diseases – overweight, (pre) diabetes type 2, lipidemia, atheroma, thrombosis,  hypertension, cancer, arthritis, dementia – is the antioxidant, insulin-sensitising, energising,  nitric-oxide-promoter, antilipidemic, antithrombogenic, antihypertensive, anti-infertility, anti-PCOS,  appetite-and-weight-suppressive,  anticancer, and diabetes-preventing   plant-derived metformin. This is the only prescription drug  ever – with zero serious persisting adverse effects in appropriate dose –    that has been  shown (including in the only 20year randomized controlled trial ever) to actually reduce all  major morbidity and all-cause mortality by over one-third.

2. Only new ie under-patent drugs are $billion dollar –a-year rainchecks in a $trillion dollar industry where only disease pays (not prevention- which keeps patients out of hospitals & specialist centres  and off new drug) .

So the Disease Industry has correctly pinpointed overweight and hypertension as the two leading risk factors to bombard consumers with new drugs;

but  has created the  gigantic marketing ploy  that these common lifestyle-diet problems  need designer drugs: that
average mild to moderate hypertension must be treated by combinations of angiotensin-and adrenergic, and calcium-blockers – which  do not reduce all-cause morbidity and mortality.;
and  even average lipid levels  by statins and now even the futile  ezetimibe –which do not reduce all-cause morbidity and mortality;
and overweight-obesity  by patented drugs like Orlistat and Rimonabant –which do not reduce all-cause morbidity and mortality  ,
and type 2 diabetes by new sulphonylureas, glitazones and even more toxic and expensive injectables  like gliptins- –which do not reduce all-cause morbidity and mortality .

But  simple analysis of the hundreds of better-quality  published studies and trials (not those ghost-written in glossy journals  for drug companies to promote their products) shows that:

For average mild-to-moderate hypertension, no modern drugs (with many serious  adverse effects)   surpass for benefit  the triple and zero-side-effect  combination of lowdose reserpine plus lowdose coamiloretic- in RSA costing retail about R45 per 4 months ie about $2/month;

For average-risk overweight adults with or without lipidemia and diabetes, nothing surpasses the global benefits- major reduction in all-cause mortality and mortality- of  metformin started in low dose eg 250mg/day and increased  slowly to tolerance.
Obviously primary prevention  for everyone includes a few grams a day of the essentials that  deplete at all ages with longevity, the degrading food chain,  pollution and stress – the natural ~50  replacement supplements of  vitamins and minerals and the human biologicals EPA+DHA, CoQ10, arginince, carnitine, n-acetyl cysteine, alphalipoic acid, taurine, carnosine, MSM, chondroglucosamine, lutein, bioflavinoid,  choline, inositol, 5HTP, GABA, melatonin, plus key plant supplements eg ginkgo, milk thistle, galega, gymnema, coleus etc;

all of which can be simply taken as a powder blend in water twice a day with a teasp of cod liver oil or a fish oil capsule;
at a global retail cost of as little as R100/$12 a month ( plus  in older people, appropriate physiological  human sex hormones).

So while there is some- but relatively little-  competition between generics, the major saving in both cost, risks and prevention is between therapeutic equivalents eg lowdose coamilozide+reserpine, metformin, and other safe effective  supplements – which are all that are needed for prevention and most treatment of all the major degenerative diseases of aging including osteoporosis  (which agents  Industry and their funded lobbyists- researchers, academics, regulators  try persistently to denigrate if not actively suppress)-  vs other newer- and heavily marketed  classes of antihypertensives, appetite ,  lipidemia and osteoarthritis-osteoporosis  suppressants.

This issue of promoting evidence-based best  therapeutic equivalents is indeed blowing against the wind, the tsunami of $billion dollar adspend by Big Business to promote their designer labels. But all countries- while  run by ruthless politician big business looking after their own interests – do pay some lip service to restraining the normative  monopolistic and price-fixing racketeering that screws the man in the street- both in gross overpricing, and in massive tax evasion by big business, and in rigging of elections and tenders .

Our own Medical Schemes Council is in the process of open consultations about the revised necessary and approved drug lists for all diseases in the medical schemes industry. Hence urgent vigorous debate is urgently required – in all countries- before vested interests further strangle citizens’ choice of and access to both cheap old drugs to eg reverse the dropping of reserpine by bureaucrats in UK, Europe and state clinics here, and reverse the rising tide of suppression of the best prevention and treatment there is- the base of all modern medicines – minerals, vitamins and the numerous proven safe human and plant biologicals.

The trend by the FDA and EU and Big Business in RSA must be reversed, before they (in the interests of their own pockets filled with paybacks by Big Pharma) put all supplements totally on prescription by health professionals- the very people whose livelihood (including their shares in Big Pharma, med schemes and hospitals) depends on new quick-fix designer drugs which cure and prevent no chronic degenerative disease ie on avoiding effective doses and combinations of proven supplements.

As it is, the medical schemes in RSA are now compelled to pay for the services of witchdoctors (who admittedly probably kill far fewer people than do modern prescriptions and surgery for non-urgent conditions) yet these schemes- while insuring for profit people who persist in suicidal and homicidal smoking and alcohol and sexual behaviour-  flatly refuse to pay for the best prevention  there is – the supplements mentioned- because  they are neither promoted by Big Pharma nor on prescription.

Numerous references are available under many keywords on this website below.

ndb

DANGEROUS MEDIA MISREPORTING ON SWINE FLU:

The media are the main cause of panic. An unsourced report being broadcast in South Africa – on the internet and our local radio- is that “According to the World Health Organisation (WHO), at least 429 people have died around the world from swine flu, which has infected 94 512 people in 136 countries”.

This is dangerous nonsense. What an authoritative report today says is  “by Monday, the total number of cases worldwide reached 94,512 — with 429 deaths — according to the World Health Organization (WHO)”.

Its all about simple English, between four-letter words:  with versus from or of

All authoritative reports indicate that the great majority of deaths are occurring in patients with serious chronic underlying disease – who commonly die anyway, often of trivial infections . Very few swine flu deaths have been in healthy young people ie attributable to swine flu virus iteslf. It has been clear for months that the swine flu is in general as highly contagious as the long-circulating other flu strains, but if anything milder; with probably millions affected- mostly untested, unreported since it is so mild.

So it is not surprising that where it is tested for, it is commonly found – eg in sick people with serious heart, lung or other immune-suppressing illness.

For unclear reasons – about which conspiracy theorists can speculate given the $trillion benefits to the disease and vaccine and antiviral industry of panic – no consolidatd report of autopsies of patients who have died with swine flu has yet been published, to establish in how many the flu was apparently the cause of death.

Until now, all authoritative reports are that vey few previously healthy people have been confirmed to have died of or from the swine flu- despite the fact that sudden death (ie from often unexpected heart attack, heart arrhythmia or stroke) is the commonest mode of sudden death – especially in the unfit ie smokers, the overweight, asthmatics, cardiacs, cancer etc…

AMERICAN GERIATRIC SOCIETY PROMOTES OPIOIDS AHEAD OF NONSTEROIDAL ANTIINFLAMMATORIES FOR PAIN..

n a landmark 1990 judgment (Ferrell 1995) , the court ruled that carers have a duty to provide pain relief even if opioids are necessary, where pain contributes materially to functional impairment and decreased quality of life.

Now the American Geriatric Society has reinforced that  (Ferrell 2009) , but warned against use of NSAIDs because of their risks, as this column argued last week starting rather with paracetamol acetaminophen +- opioid as backup.

ndb