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..

A  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 disease” Due 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

I was bobbing chest deep in the Adriatic when one of my students asked about job prospects. Since most of the veteran journalists I know are glad to have a job at all (if they, in fact, are still employed) it is hard to come up with a rosy projection for someone in J-school. Heck, half the papers can’t even afford interns.

This program is about giving students as many skills as possible to make them desirable candidates. But really, are they hoping for newsroom jobs? I hope not. Is being a “backpack journalist” a long-term career aspiration? I am not sure.

This column from David Westphal on OJR.org praises Jason Motlagh as the future of entrepreneurial journalism. Motlagh is a freelance foreign correspondent piecing together a living. Westphal writes:

 

But that rendition of Motlagh’s recent work doesn’t get at the heart of what he does or what makes it work. Here’s what’s telling:

 

• He’s a multimedia journalist. Motlagh doesn’t just write stories. He shoots still photos. He shoots and edits video. He does audio. He blogs. He narrates slide shows. And because he does all of those things, he says, he has a huge advantage over free-lance foreign correspondents working in a single medium. Having multiple media skills is “still unusual,” he said. “There aren’t a whole lot of people yet who have gotten up to speed. If you are, you can make clients an offer they can’t refuse.”
• He’s an entrepreneur. This isn’t a new part of a free-lancer’s life, but it’s becoming increasingly important as traditional clients fall by the wayside. In the last two years he lost two important outlets in the San Francisco Chronicle and U.S. News & World Report. But landing work at the Pulitzer Center, and increasing billings through his multimedia work, fills the gaps.
• He lives modestly and accepts that there may be periods in his work where he’ll have to do something besides journalism to pay the bills.

This question of compensation is something that bedeviled my class at the USC Annenberg School for Communication last semester. Students were thrilled with Jon Sawyer’s presentation about the Pulitzer Center – some of them were ready to go abroad immediately – but were stumped about how they would live when Pulitzer essentially pays only travel stipends (usually $1,500 to $5,000).

As a homeowner with family aspiration, I find it hard to reconcile that striking out on crazy adventures is the only way that one might be able to be successful in this business in the future. 

But I do like the part where he says that learning video journalism could be the ticket on to the trolley moving forward.

Enrico Rava

Dal 9 al 12 luglio torna il festival jazz diretto da Onofrio Piccolo. Nella location del Parco Pubblico di Pomigliano D’Arco,  parte la XIV edizione di uno degli eventi più attesi dell’estate campania, sia per la qualità degli artisti in programma, che per la sperimentazione e valorizzazione del territorio. E poi è gratis.

Dalle 21 alle 2 di notte tre concerti ogni sera,  poi workshop, incontri, jam e tanto altro. Ovviamente ingresso gratuito.

Si parte il 9 luglio con Marco Zurzolo in “Migranti”, poi la tromba di Enrico Rava New Quintet con Gianluca Petrella e Eivind Aarset Sonic Codex Quartet. Il 10 Stefano Battaglia trio in “Re: Pasolini2, poi Martux_M con Bosso, Bearzatti, Aarset e Vigorito in “About A Silent Way” e Mario Raja Bing Bang.

Sabato 11 luglio sul palco saliranno William Parker Chamber Trio e Anthony Braxton Diamond Curtain Wall Trio, ed infine l’Orquestra Imperial, ensemble che racchiude alcuni tra i più rappresentativi musicisti brasiliani: Moreno Veloso (figlio del grande Caetano), Kassin, Domenico Lancelotti, Wilson Das Neves, Berna Ceppas, Nina Beker e Rodrigo Amarante . Chiusura il 12 con l’Orchestra Napoletana di Jazz (già ospite lo scorso anno) feat. Raiz , Joe Lovano, Capone, Famoudou Don Moye e Ada Montellanico.  Sul palco anche Giuseppe La Pusata Trio “Naissance” e
Francesco Marziani, Mariano Bellopedem Franco Piccinno in solo piano.

Inoltre ci saranno le guida all’ascolto, i seminari sul jazz quest’anno dedicati a Billie Holiday, Chet Baker, Kind Of Blue di Miles Davis e a Michael Petrucciani.

il sito ufficiale