Tag Archives: osteonecrosis

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

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.

UPDATE: WHY TAKE BISPHOSPHONATES OR ANY SYNTHETICS FOR OSTEOPOROSIS?

 as this column has previously discussed,  osteoporosis fracture prevention requires nothing but a sensible lifestyle plus sensible  lowcost  permanent cocktail of natural supplements that reverse all chronic degenerative diseases- eg calmag, boron, zinc, manganese; vits B C D & K,  proline, and lowdose appropriate  HRT. Better late than never, but the earlier started the better.

 

The  heavily marketed commercial moneyspinners-  bisphosphonates BNPs; strontium ranelate; calcitonin, parathormone, SERMs eg raloxifene; tibolone; and statins – each have significant risks and costs, and none give  the multisystem protection of the scores of  evidence-based natural supplements.

 

          The reviews and trials  of bisphosphonates the last year  are especially alarming for zoledronic acid (ZA Reclast / Zometa)   

Today’s FDA  (Grewal) last month reports that ZA and Aredia give an osteonecrosis (O.N) risk of about 1:10 000 patients; alendronate a risk of 0.7/ 100 000 patient years.

this year Italy  (Ibrahim) reports an incidence of 1.5% ONJ in 500 cancer patients over 4yrs- and all those patients were treated with ZA.

Harvard Dental School  (Wessel) this year reports 30 cases of  O.N of the jaw ONJ over 4 years – all on ZA.

But Univ Arizona  (Hess) this year reports  99 cases of ONJ after bisphos in patients without cancer- 85 for OP, 10 for Pagets. 87% were women and 83%  had  oral not  iv BNP.

 

The international HORIZON Z.A.osteoporosis  trials last year reported 1 case of O.N   in each  2500  arm of trialists  on ZA or placebo (mean 74yrs (65-85yrs)  treated with annual  ZA versus placebo injection; there was  35% reduction in fracture rate at  mean followup 1.9years  in those  enrolled after hip fracture ie tertiary prevention ;

  and 70%  fewer fractures at 3yrs in women enrolled with osteoporosis.- secondary prevention  (ZA 1.1%pa, placebo 3.6%pa).

      There was  however no significant difference in major adverse events or non-fracture deaths (the causes of death of  the majority. were not reported).  However, serious atrial fibrillation was 3 times more common in the month after ZA than after placebo.  By  1.9yrs after the hip fracture and starting ZA  there were fewer deaths on ZA 4.5%pa than placebo 6.7%;  but in the slightly younger and fitter majority ie  those without  prior hip fracture, by  3 yrs, there were 16% more deaths on ZA (1.13%pa%) than placebo(0.97%pa%).

    These 2007 Horizon trials  thus highlight that delaying prevention  till the hip collapses more than trebles the deathrate .

     What they  mysteriously neglect to  report is the quality of life, mobility after major osteoporotic fracture- when it is common cause that waiting for major disease before starting prevention is disastrous- sudden death, stroke, dementia; or that at best 20% of patients  recover full health and mobility after hip fracture.

 

          However, (as usual with commercially sponsored trials to promote a new drug – ie seeding trials) baseline conventionally proven natural therapies were severely limited, probably to falsely exaggerate the benefit of the trial drug:  so  (while almost half were apparently on raloxifene), all  including the placebo arm were given a baseline  regime only of vitamin D and modest dose calcium.

          The Sponsors  thus chose to ignore the longstanding evidence from major studies and trials –  that no designer drugs are needed to reduce both osteoporotic fractures and most all-cause aging diseases: – merely appropriate supplement/ replacement with, calcium, magnesium, zinc, boron, manganese, all 13 vitamins and the biologicals ( proline,  lowdose appropriate sexhormones, fish oil  – and  for other multisystem protection,  eg arginine, carnitine, CoQ10,  glucosamine, chondroitin, MSM etc.).

 

    While it is common cause that quality of life QOL  is greatly improved by appropriate HRT in the menopause transition- the midlife decade of menopause symptoms ,

      longterm QOL outcome is  conveniently not mentioned in any bisphosphonate papers that span the progressively more risky  decades after the midsixties –  although this QOL attribute for ZA is a main goal that  Novartis mentions in it’s registration motivation   ” The unique  once-yearly dosing of this medicine has the potential for significant compliance benefits and improved quality of life for women with osteoporosis.”  

 

        Despite the fact that trials of bisphosphonates for osteoporosis started over 20 years ago, no such claim of improved mobility and QOL long term  is made, so there cannot have been any significant improvement shown.  There are exactly two  small trials, from Italy and Turkey,  that lasted one year looking at QOL, that showed improvement in QOL on (alendronate or   nerindronate or calcitonin)  plus calcium/vit D versus calcium/vit D alone. Short term study- one year – says nothing about the average 35yrs of life expectancy after the perimenopausal midlife decade. .

 

 The bisphosphonate trials also blithely omit  that the top risk factor for osteoporotic fractures is not bone density but overall  physical – frailty, falls; and while  major fractures are common in the old, they dont happen,if the patient dies early,  or they  matter little if the patient is first disabled (before fracturing) by far more common cardiovascular-stroke problems or dementia.

     Nobody can claim, show  that bisphosphonates, SERMS, tibolone, calcitonin, strontium have any significant long term benefit on overall premature major diseases of aging and mortality.  Unlike appropriate HRT, or fish oil, or metformin, or vigorous other combination of natural supplements (vitamins, minerals and  biologicals including herbs) , no modern chronic designer patent drug  for chronic prevention has been shown to  significantly reduce all-cause morbidity and mortality – especially diabetes, CVD-stroke, osteoarthritis, fractures, major depression and dementia. .

 

    So there is no justification or need  to take bisphosphonates or any other newer patent drugs for osteoporosis – and why take the risk of bisphosphonate arrhythmia, toxicoderma  or osteonecrosis?

THE CRIMINAL BIPHOSPHONATE DECEPTION

BONE BOOSTERS? Biphosphonates BNPs NDB 2007 updated 19 March 2008; 6 April 2008

No trials have ever been published showing that biphosphonates do overall good long term for osteoporosis- ie reduce all-cause mortality, and reduce hip fracture, without toxicity.
Biphosphonate Osteonecrosis of long bones was already published in 1995, and from 2001 in USA.
So their heavy marketing, and prescription like vitamins, causing the epidemic of devastating osteonecrosis, makes the prescribers, manufacturers, dispensers and Regulators – eg the FDA -criminally liable.

Effects of continuing ALENDRONATE after 5 years of treatment: Fracture Intervention Extension to 10yrs
JAMA. 2006 Black, Cummings UCSF. (who funds them?!)
In 1099 women re-randomized to alendronate or placebo for a further 5 years (1998-2003):

Continuing alendronate halved only recognized vertebral fracture risk (2.4% vs 5.3% for placebo);

their conclusion: “women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years”. Ie no benefit for the far more important hip bones.

But was this a dangerous lie?
the 19% Risk of nonvertebral fractures was no different (RR 1 ) between continuing and discontinuing alendronate.

“Susan Ott (JCEM Mar 2005) already questioned bisphosphonate long term safety”

Biphosphonate BPN Jaw OSTEONECROSIS ONJ is now endemic worldwide:
1st reported in 1994 (Guanabens, Spain- leg stress #s),
2001-03 – USA 63 cases (Ruggiero 2004)
(2002-5 Pozi) Italy- 35 ;
(2003-5 (Abu-Id 2006) Germany 73 cases
2004-5 (Mavrotoki) Australia 158

by July 2006 over 3000 cases of ONJ were reputedly already reported.

“of Odvina‘s 9 cases of spontaneous fractures on alendronate –
5 were mid-femur fractures (2 bilateral same as Toulouse).
6 had delayed or absent fracture healing.

Estrogen alone is anabolic only on bone, uterus, memory, fat – If anything it both builds inner hostility, fattening, inflammation,
& wastes collagen ie muscle catabolic – thus doubles incontinence.

The only true anabolics (ie strengthen muscle, melt fat) are
* food incl vita-/minerals incl. vitamin C/D; CoQ10, carnitine,
* Insulin sensitizers – metformin; natural androgens, exercise.

Dach: “ Look at Toulouse Lautrec.. His parents were first cousins…
” we are giving women Toulouse Lautrec’s bone disease- the same jaw necrosis, mid-femur fractures, failure of bone healing,

“ But women who sustain fractures on BPNs are told that the fractures are due to the underlying osteoporosis, not the drug”
http://www.drdach.com/wst_page6.html

The osteonecrosis problem may be 95% with iv BPNs (Urade) – orally BNPs like HRT are absorbed below 10%;
but
as with oral HRT, the problem may be both total dose absorbed, and total length of exposure –BPNs (given over perhaps a year iv) bind to bone for 10yrs. Fosamax is swallowed for 3-5yrs.
Jones & Wilkinson’s (April 2006 NHS review of oral BPN adversity) found that adherence on oral BPNs is only around 50% by 3 years due to adversity – GIT, musculoskeletal, skin….
and when stopped, BMD is maintained for up to 2 yrs due to bound Testosterone (unlike estrogen).

Is there (as there was with tobacco, Premarin & Vioxx)
a BMD industry OSTEOPOROSIS FRACTURE DECEPTION?

The OSTEOPOROSIS FRACTURE DECEPTION?:

The chief risk factor for fractures is not BMD, osteoporosis,

but immobility, falls, inco-ordination, muscular frailty = sarcopenia
– which in turn limits exercise, endurance, motivation.

By contrast,
permanent appropriate TRT in men and T+ E2RT in women can prevent eg the up to 40% bone loss that occurs in 6 months on corticosteroids (Studd 1989),

restore up to 26% of lost BMD in critical areas like Ward’s triangle ie (the hipbone’s neck);

of the 6 published RCTs that have given testosterone replacement (with or without estrogen) for 1-2 years post menopause, 5 showed that testosterone gave better increase in BMD than estrogen alone.
In the 6th and oldest study (Studd 1992) in women both with and without hysterectomy, adding implants of testo 75mg 6mthly to Esto 100mg 6mthly made no difference over esto alone, possibly because the of the supraphysiological esto level attained (mean ~1.9nmol/L per Studd 2006) and the followup of only 1year.

In the 7th trial of only 6 months(2005), no improvement was seen in BMD on either esto alone or on Esto + testo- but it used oral HRT; lean mass increased only on the combination- so these women would have been less prone to falls and fractures. .

On the baker’s dozen of natural supplements, we have seen bone density increasing steadily by 1% a year – slightly faster in spine than hip- over 15 years in eg a severely osteoporotic woman with chronic active rheumatoid arthritis on prednisone.

After osteonecrosis the results with hyperbaric oxygen added to the natural supplements appear useful to justify it’s use to salvage whats left ..

HRT AND FRACTURES:

IN the Women’s Health Initiative,

the fracture rate in those with womb was 0.15%pa,
and E+P reduced this by 34% over 5.6yrs;

in those post hysterectomy ie longer without hormones,
the fracture rate was 0.17%pa,
and E alone reduced this by 39% ie 60% still had long bone fractures.

No trials have measured fracture rate on TRT in women;
but we never see women on TRT have spontaneous limb fracture.

Only androgen improves muscle strength;
HRT suppresses relative androgen levels.
so why must women go without replacement androgen?

ndb

Use of platelet-rich plasma in the management of oral biphosphonate-associated osteonecrosis of the jaw: a report of 2 cases. J Oral Implantol. 2007;33:371-82 Lee CY, ea
Bisphosphonates (BP) are nonhormonal medications used in the treatment of various bone malignancies and metabolic conditions. Since 2003, there have appeared a significant and growing number of articles in the worldwide medical and dental literature describing the complication of an osteonecrosis of the jaws associated with the intravenous and, most recently, the oral form of BP medication that has been refractory to any definitive form of treatment. The authors have successfully managed 2 patients taking the oral form of BP with adjunctive treatment using platelet-rich plasma (PRP), and in one case with hyperbaric oxygen (HBO). We were able to obtain complete remission in each case, which is defined as resolution of pain and complete closure of exposed bone in the jaws. The purpose of this report is to describe a treatment protocol and the rationale for using PRP and HBO to obtain complete remission of this new pathologic condition.

Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series.J Oral Maxillofac Surg. 2007 Jul;65(7):1275-6. Freiberger JJ, Padilla-Burgos R, Chhoeu AH, Kraft KH, Boneta O, Moon RE, Piantadosi CA.Duke University Medical Center, Divers Alert Network, Durham,.
PURPOSE: Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) is an emerging problem with few therapeutic options. Our pilot study of BP-ONJ investigated a possible role for hyperbaric oxygen (HBO(2)) therapy. PATIENTS AND METHODS: A total of 16 patients, ranging in age from 43 to 78 years, with BP-ONJ were treated with adjunctive HBO(2) between July 2003 and April 2006. Staging was based on the size and number of oral lesions. Clinical response after treatment and at distant follow-up; the odds of remission, stabilization, or relapse; and time to failure analysis were calculated. RESULTS: The median time on BP therapy before appearance of ONJ symptoms was 18 months, and that from symptom onset to HBO(2) therapy was 12 months. Fourteen of 16 patients (87.5%) improved in stage. The size and number of ONJ lesions were decreased after HBO(2) therapy (P < .001 and P = .008, respectively; Wilcoxon signed-rank test). Immediately after HBO(2) therapy, 7 of 16 patients (44%) were in remission and 8 (50%) had stabilized; however, stabilization without remission was sustained in only 2 patients. At follow-up, 10 of the patients (62.5%) were still in remission or had stabilized. The 7 patients who continued on BP treatment during HBO(2) therapy had a shorter time to failure (8.5 months; 95% confidence interval [CI] = 7.1 to 9.8) than those who discontinued the drug (20.1 months; 95% CI = 17.5 to 23.9; P = .006 by the log-rank test). Clinical response was not associated with cancer type or malignancy remission status. CONCLUSIONS: Adjunctive HBO(2) therapy may benefit patients with BP-ONJ; however, the outcome is improved with cessation of BP administration.

3: Am J Otolaryngol. 2007 May-Jun;28(3):158-63.
Osteonecrosis of the jaws due to bisphosphonate use. A review of 60 cases and treatment proposals.
Magopoulos C, Karakinaris G, Telioudis Z, Vahtsevanos K, Dimitrakopoulos I, Antoniadis K, Delaroudis S. Aristotle University, Thessaloniki, Greece.
PURPOSE: Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. In the last two and a half years, there has been a striking increased referral of patients with exposed necrotic jawbone, mostly after several teeth extractions. The only clinical feature common in all patients was the use of bisphosphonates in the treatment of bone diseases. PATIENTS AND METHODS: We performed a retrospective multicentric study of 60 patients with necrotic bone lesions of the jaws of various extent from July 2003 to October 2005. The necrotic bone involved the maxilla (37%), the mandible (50%), or both (13%). The bisphosphonate administered was mostly zoledronate. The management of the patients included cessation of bisphosphonate therapy for more than 6 months, long-term antibiotics, hyperbaric oxygen administration in some cases, and various surgical restorative procedures. RESULTS: The implementation of the treatment protocol in 7 patients so far lead to high cure rates, whereas surgical restoration of the defect without previous cessation of bisphosphonate therapy had discouraging results. CONCLUSIONS: Clinicians and dentists should have in mind this new complication of bisphosphonate administration to identify and treat osteonecrosis of the jaws.