SLA Biomedical & Life Sciences Division Blog

The Bisphosphonates: Fosamax™, Actonel™, Actonel with Calcium ™, Boniva™, Atelvia™ , Reclast™, Skelid™ & Zometa™. Vastly more helpful for millions by reducing the threat of osteoporosis than surely more harmful for a very few

 

What are the bisphosphonates?

The bisphosphonates are a class of drugs that are generally prescribed, primarily for women who are late pre-menopausal, menopausal or post-menopausal to reduce and possibly reverse the demineralization of bone through calcium loss, usually targeting the two areas of the body where calcium loss causes the most damage: the spinal column (vertebrae) and the hip and thigh. They are also prescribed for certain cancers (mostly myeolomas, but also metastases from breast cancer in women and prostate cancer in men ), and diseases (Paget’s Disease, Osteogenesis Imperfecta,  AIDS, certain types of renal failure) which have the direct unfortunate effect of inducing bone thinning and fractures  of themselves, or which involve treatments that have those adverse side effects.

Why are these drugs  in the news?

On October 13, 2010, the US Food & Drug Administration added some new information to be given to patients taking these medications, as well as to their prescribing physicians. It concerns a potential for a somewhat higher statistical chance for certain rare types of hip and thigh bone fractures for those who have been taking bisphosphonates for several years vs. the overall incidence of vertebral, hip and thigh fractures.

Why would this be news?

It most likely became news primarily because we as a public in the United States and perhaps elsewhere in the developed world, have become almost paranoid about drug recalls, and are often morbidly entertained by conspiracy thinking about “Big Pharma” and doctors who prescribe drugs allegedly because they are incentivized with free vacations, subsidized continuing medical education junkets, or some other type of underhanded inducements. Less than a month earlier, Avandia™ , a drug given to diabetics to forestall heart disease (ironically diabetes is not the direct cause of death for the vast majority of diabetics, the number one direct killer of diabetics is actually heart disease) counter-intuitively actually increased the chances of a small, but significant number of Avandia™-taking patients, to develop heart disease, and therefore was severely restricted.

What actually did the FDA advisory say to patients about these bisphosphonates?

On its website, www.fda.gov/Drugs/DrugSafety/ucm229009.htm the FDA advises patients to:

• Continue to take your medication unless you are told to stop by your healthcare professional.

 

• Talk to your healthcare professional if you develop new hip or thigh pain (commonly described as dull or aching pain), or have any concerns  with your medications.

 

• Report any side effects with your bisphosphonate medication to FDA’s Medwatch program using the information at the bottom of the page in the “Contact Us” box.  

 

What did the FDA advisory say to Doctors about these bisphosphonates?

On its website, www.fda.gov/Drugs/DrugSafety/ucm229009.htm the “FDA recommends that healthcare professionals should:

• Be aware of the possible risk of atypical subtrochanteric and diaphyseal femur fractures in patients taking bisphosphonates.

 

• Continue to follow the recommendations in the drug label when prescribing bisphosphonates.

 

 

• Discuss the known benefits and potential risks of using bisphosphonates with patients.

 

 

• Evaluate any patient who presents with new thigh or groin pain to rule out a femoral fracture.

 

 

• Discontinue potent antiresorptive medications (including bisphosphonates) in patients who have evidence of a femoral shaft fracture.

 

 

• Consider periodic reevalutation of the need for continued bisphosphonate therapy, particularly in patients who have been treated for over 5 years.

 

 

• Report any adverse events with the use of bisphosphonates to FDA’s MedWatch program using the information at the bottom of the page in the “Contact Us” box.

 

Any information provided to MedWatch should be as detailed as possible and include information concerning fracture location/configuration, magnitude of trauma, fracture details (complete or incomplete, bilateral, or comminuted), presence and duration of prodromal thigh or groin pain, duration of bisphosphonate use, relevant medical history, and concomitant use of other medications. “

What is the key point involved in these advisories?

There appears to be a tiny  increase in the relative (but not necessarily absolute) number of subtrochanteric and femoral shaft fractures, largely  in elderly women taking one of the bisphosphonates for several years. Depending on your means of calculating odds with the worst case statistics, this means that there is a worst case possibility that 3%-5% of all the patients at high risk for an osteoporosis-related fracture might get a different and fairly rare (“atypical” is the term used) fracture farther down the thigh than the usual location for such fractures, and it would be wise to monitor them for dull pain in the thigh and/or groin  if they have been taking bisphosphonates for a long time (several years), because most patients (70%) who eventually have such a fracture had this tell-tale symptom first.

Does this mean that not taking bisphosphonates actually decreases your chance of getting a vertebral, hip  & thigh fracture?

Absolutely not! Probably the best estimate, taken from  Shane et al (2010) is that prescription bisphosphonates cut the number of vertebral fractures by 1000/10,000 patient years and the number of hip and thigh fractures by 700/10,000 patient years. This is an astonishingly positive  benefit to risk ratio. Quite literally millions of people have benefited from taking these drugs, while at the worst perhaps 300-400  cases drawn from about 170 pooled articles,  have been documented in the medical literature as having these rare fractures or other complications, in conjunction with their taking bisphosphonates .

Are there any confounding conditions connected with the women taking bisphosphonates and subsequently having one of these atypical fractures?

Yes, while the number of studies and case reports are scattered and do not all follow the same protocols for diagnosis and classification of these traumas, it appears, that a  fair number were older and  in generally poorer health, had been using proton pump inhibitors for gastric reflux,  had a history of osteoarthritis, had previous bone fractures and in some cases had taken cancer chemotherapeutic or immunosuppressive drugs. In other words, they had rather lengthy prior histories of medical importance. There is also some suggestion that Asian women were at greater risk.  However, other studies of women without all these complications or predispositions, or with matching records of having them to the same degree,  still show some increased risk of having these atypical fractures. There is little doubt that the risk of these atypical fractures is real, but significant doubt as to just how small the number of affected individuals might be when compared to the overall pool of people at risk for osteoporosis-related fractures: 5%?, 4%, 3%?, 2%?, 1%?,  0.1%, 0.01%? To determine better just what the odds are, and to track what happens when the bisphophonates are discontinued at the earliest signs of trouble, a registry of cases is being proposed (Shane et al 2010). Nonetheless, no fewer than 20 of the articles cited below still regard prescription bisphosphonates as the strategy of choice for patients seriously at risk for osteoporosis-related fractures.

What about bisphosphonates might be causing this small number of atypical fractures?

Fractures from osteoporosis related  causes tend to be  owing to the thinning  of the cortical (outermost) structural layer of bone, and/or from accumulating defects in the microarchitecture of the minerals in the bone. Bisphosphonates may be better at strengthening the cortical thickening than they are at repairing microarchitecture, or the methods or route  by which they strengthen the cortex has the unintended side-effect of further weakening the microarchitecture.  This microarchitecture  weakness would make help us make sense of the tiny minority of patients who also have a necrotic reaction to bisphosphonates that manifests itself in the jaw to the degree that it causes the drug’s discontinuance, and makes dental procedures problematic.  (But even in the cases of jaw misadventure, the patients are older, poorer, and sicker on average). In other words, bisphosphonates may not be the perfect medicine for this condition, albeit they are the best we currently have in production and have been proven safe and effective for millions thus far.

So, should we not be glad that the FDA stopped this "Big Pharma" conspiracy?

Well, even the worse conspiracy theorists would be dumbfounded when they learn that 21 of the 23 researchers involved in the key  Task Force of the American Society for Bone and Mineral Research overview (Shane et al 2010) on which the FDA’s modified patient and physician advisories were based,  either worked for, or had taken funding from, those allegedly evil folks in Big Pharma. It is little understood by many in the investigative reporting business that sometimes the greatest pool of expertise really does come from people who do research within or are funded by,   businesses who generally make our lives much better, because developing new drugs that help us manage or cure diseases is pretty much their life’s work.

What would be the most likely health outcomes if people were scared off taking their bisphosphonates by overhyped media reports?

Funny that you should ask, because a study of this has already been done in Australia where medical and prescription drug records are available to researchers owing to governmental benefits programs. According to Sambook et al 2010, adverse media reports on the side effects and risks for bisphosphonates appearing in Australia last year probably resulted in the ensuing nine months in 70 more hip fractures, 60 more other fractures (largely vertebral) and 14 more deaths, than would have occurred if the patients had simply stuck to taking them.

Tony Stankus FSLA [email protected] Life Science Librarian, Science Coordinator &  Professor,

Editor-in-Chief of Science & Technology Libraries

University of Arkansas Libraries MULN 233 E

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Antoniazzi, Franco, Elena Monti, Giacomo Venturi, Roberto Franceschi, Francesco Doro, Davide Gatti, Giorgio Zamboni, and Luciano Tatò. 2010. GH in combination with bisphosphonate treatment in Osteogenesis Imperfecta. European Journal of Endocrinology / European Federation of Endocrine Societies 163 (3) (09): 479-87.

Baqain, Zaid H., Faleh A. Sawair, Zaid Tamimi, Nazzal Bsoul, Ghazi Al Edwan, Jamal K. Almasad, and Abdalla A. Abbadi. 2010. Osteonecrosis of jaws related to intravenous bisphosphonates: The experience of a Jordanian teaching hospital. Annals of the Royal College of Surgeons of England 92 (6) (09): 489-94.

Barney, Rocky J., Brian M. Wasko, Amel Dudakovic, Raymond J. Hohl, and David F. Wiemer. 2010. Synthesis and biological evaluation of a series of aromatic bisphosphonates. Bioorganic & Medicinal Chemistry 18 (20) (10/15): 7212-20.

Beukelman, T., K. G. Saag, J. R. Curtis, M. L. Kilgore, and M. Pisu. 2010. Cost-effectiveness of multifaceted evidence implementation programs for the prevention of glucocorticoid-induced osteoporosis. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (9) (09): 1573-84.

Bladé, J., M. T. Cibeira, de Larrea Fernández, and L. Rosiñol. 2010. Multiple myeloma. Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO 21 Suppl 7 (10): vii313-9.

Bleicher, Kerrin, Vasi Naganathan, Robert G. Cumming, Markus J. Seibel, Philip N. Sambrook, Fiona M. Blyth, David Le Couteur G., David J. Handelsman, Louise M. Waite, and Helen M. Creasey. 2010. Prevalence and treatment of osteoporosis in older Australian men: Findings from the CHAMP study. The Medical Journal of Australia 193 (7) (10/04): 387-91.

Body, J-J. 2010. Prevention and treatment of side-effects of systemic treatment: Bone loss. Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO 21 Suppl 7 (10): vii180-5.

Brandi, Maria Luisa. 2010. Current treatment approaches for Paget's Disease of Bone. Discovery Medicine 10 (52) (09): 209-12.

Brown, Janet E., and Sheryl Sim. 2010. Evolving role of bone biomarkers in castration-resistant prostate cancer. Neoplasia (New York, N.Y.) 12 (9) (09): 685-96.

Canoui-Poitrine, F., S. Jaglal, R. Chapurlat, V. Tainturier, C. Colin, and A. M. Schott. 2010. Has reimbursement of bone mineral density testing and anti-osteoporotic treatments improved management of osteoporosis in France? Bone 47 (4) (10): 790-4.

Cardwell, Chris R., Christian C. Abnet, Marie M. Cantwell, and Liam J. Murray. 2010. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA: The Journal of the American Medical Association 304 (6) (08/11): 657-63.

Castellví, Ivan, Maria Bonet, Jose Narváez A., and Jose Molina-Hinojosa. 2010. Successful treatment of SAPHO syndrome with adalimumab: A case report. Clinical Rheumatology 29 (10) (10): 1205-7.

D'Amelio, P., A. Grimaldi, M. A. Cristofaro, M. Ravazzoli, P. A. Molinatti, G. P. Pescarmona, and G. C. Isaia. 2010. Alendronate reduces osteoclast precursors in osteoporosis. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (10) (10): 1741-50.

Diel, Ingo J., Andreas H. A. Kurth, Hans-Bernd Sittig, Harald Meden, Michael Maasberg, Andreas Sandermann, and Raoul Bergner. 2010. Bone pain reduction in patients with metastatic breast cancer treated with ibandronate-results from a post-marketing surveillance study. Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer 18 (10) (10): 1305-12.

Dissette, Valeria, Pietro Bozzi, Carlo Alberto Bignozzi, Alessandro Dalpiaz, Luca Ferraro, Sarah Beggiato, Eliana Leo, Eleonora Vighi, and Luisa Pasti. 2010. Particulate adducts based on sodium risedronate and titanium dioxide for the bioavailability enhancement of oral administered bisphosphonates. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences 41 (2) (10/09): 328-36.

Duque, Gustavo, Jacqueline J. Close, Julien de Jager P., Peter R. Ebeling, Charles Inderjeeth, Stephen Lord, Andrew J. McLachlan, Ian R. Reid, Bruce R. Troen, and Philip N. Sambrook. 2010. Treatment for osteoporosis in Australian residential aged care facilities: Consensus recommendations for fracture prevention. The Medical Journal of Australia 193 (3) (08/02): 173-9.

Epstein-Barash, Hila, Dikla Gutman, Ela Markovsky, Galit Mishan-Eisenberg, Nickolay Koroukhov, Janos Szebeni, and Gershon Golomb. 2010. Physicochemical parameters affecting liposomal bisphosphonates bioactivity for restenosis therapy: Internalization, cell inhibition, activation of cytokines and complement, and mechanism of cell death. Journal of Controlled Release: Official Journal of the Controlled Release Society 146 (2) (09/01): 182-95.

Garg, Arun. 2010. News on bisphosphonates: But will patterns of use change? Dental Implantology Update 21 (9) (09): 71-2.

Gimsing, Peter, Kristina Carlson, Ingemar Turesson, Peter Fayers, Anders Waage, Annette Vangsted, Anne Mylin, et al. 2010. Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): A double-blind, randomised controlled trial. The Lancet Oncology 11 (10) (10): 973-82.

Giovannini, Monica, Daniela Aldrighetti, Patrizia Zucchinelli, Carmen Belli, and Eugenio Villa. 2010. Antiangiogenic strategies in breast cancer management. Critical Reviews in oncology/hematology 76 (1) (10): 13-35.

Guañabens, Núria, and Albert Parés. 2010. Liver and bone. Archives of Biochemistry and Biophysics 503 (1) (11/01): 84-94.

Harel, Ran, and Lilyana Angelov. 2010. Spine metastases: Current treatments and future directions. European Journal of Cancer (Oxford, England: 1990) 46 (15) (10): 2696-707.

Haworth, Charles S. 2010. Impact of cystic fibrosis on bone health. Current Opinion in Pulmonary Medicine 16 (6) (11): 616-22.

Hofbauer, Lorenz C., Franz Jakob, and Dieter Felsenberg. 2010. Bisphosphonates and atypical femoral fractures. The New England Journal of Medicine 363 (11) (09/09): 1084; author reply 1084-5.

Holmberg, Anders R., Ulf H. Lerner, Ayodele A. Alayia, Mai Al-Mohanna, Chaker Adra, Marcela Marquez, Lennart Meurling, and Sten Nilsson. 2010. Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis. International Journal of Oncology 37 (3) (09): 563-7.

Iguchi, Kazuhiro, Yoshiki Tatsuda, Shigeyuki Usui, and Kazuyuki Hirano. 2010. Pamidronate inhibits antiapoptotic bcl-2 expression through inhibition of the mevalonate pathway in prostate cancer PC-3 cells. European Journal of Pharmacology 641 (1) (09/01): 35-40.

Imaz, I., P. Zegarra, J. González-Enríquez, B. Rubio, R. Alcazar, and J. M. Amate. 2010. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: Systematic review and meta-analysis. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (11) (11): 1943-51.

Jones, Michael D., Charles W. Tran, Guang Li, Walter P. Maksymowych, Ronald F. Zernicke, and Michael R. Doschak. 2010. In vivo microfocal computed tomography and micro-magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat. Arthritis and Rheumatism 62 (9) (09): 2726-35.

Jules, Joel, Jason W. Ashley, and Xu Feng. 2010. Selective targeting of RANK signaling pathways as new therapeutic strategies for osteoporosis. Expert Opinion on Therapeutic Targets 14 (9) (09): 923-34.

Kaji, H., Y. Kuroki, Y. Murakawa, I. Funakawa, Y. Funasaka, F. Kanda, and T. Sugimoto. 2010. Effect of alendronate on bone metabolic indices and bone mineral density in patients treated with high-dose glucocorticoid: A prospective study. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (9) (09): 1565-71.

Karosas, Ann O. 2010. Ewing's sarcoma. American Journal of Health-System Pharmacy: AJHP: Official Journal of the American Society of Health-System Pharmacists 67 (19) (10/01): 1599-605.

Katsumi, Hidemasa, Kosuke Kusamori, Toshiyasu Sakane, and Akira Yamamoto. 2010. Development of delivery system of bisphosphonates for the treatment of osteoporosis. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan 130 (9) (09): 1129-33.

Lamberg, A. L., E. Horvath-Puho, S. Christensen, and Sørensen H.T. 2010. Use of oral bisphosphonates and risk of venous thromboembolism: A population-based case-control study. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (11) (11): 1911-7.

Lazarovici, Towy Sorel, Shlomit Mesilaty-Gross, Iris Vered, Clara Pariente, Hannah Kanety, Navot Givol, Ran Yahalom, Shlomo Taicher, and Noam Yarom. 2010. Serologic bone markers for predicting development of osteonecrosis of the jaw in patients receiving bisphosphonates. Journal of Oral and Maxillofacial Surgery: Official Journal of the American Association of Oral and Maxillofacial Surgeons 68 (9) (09): 2241-7.

Lipton, Allan. 2010. New approaches to treating and preventing bone metastases. Current Opinion in Supportive and Palliative Care 4 (3) (09): 178-81.

López-Jornet, Pía, Fabio Camacho-Alonso, Francisco Molina-Miñano, Francisco Gómez-García, and Vicente Vicente-Ortega. 2010. An experimental study of bisphosphonate-induced jaws osteonecrosis in sprague-dawley rats. Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 39 (9) (10): 697-702.

Lyritis, George P., Thomas Georgoulas, and Christos P. Zafeiris. 2010. Bone anabolic versus bone anticatabolic treatment of postmenopausal osteoporosis. Annals of the New York Academy of Sciences 1205 (1) (09): 277-83.

Magrey, Marina, and Muhammad Asim Khan. 2010. Osteoporosis in ankylosing spondylitis. Current Rheumatology Reports 12 (5) (10): 332-6.

Mahtani, Reshma, and Mohammad Jahanzeb. 2010. Bisphosphonates as anticancer therapy for early breast cancer. Clinical Breast Cancer 10 (5) (10/01): 359-66.

Maricic, Michael. 2010. The role of zoledronic acid in the management of osteoporosis. Clinical Rheumatology 29 (10) (10): 1079-84.

McKague, Meredith, Derek Jorgenson, and Kelly A. Buxton. 2010. Ocular side effects of bisphosphonates: A case report and literature review. Canadian Family Physician Médecin De Famille Canadien 56 (10) (10): 1015-7.

Mehanna, P., and R. Goddard. 2010. Bisphosphonate associated osteonecrosis: An unusual case. Australian Dental Journal 55 (3) (09): 311-3.

Miller, P. D., and R. J. Derman. 2010. What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis? Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (11) (11): 1793-802.

Odri, Guillaume A., Sophie Dumoucel, Gaëlle Picarda, Sé Battaglia, François Lamoureux, Nadège Corradini, Julie Rousseau, et al. 2010. Zoledronic acid as a new adjuvant therapeutic strategy for Ewing's Sarcoma patients. Cancer Research 70 (19) (10/01): 7610-9.

Oldfield, Eric. 2010. Targeting isoprenoid biosynthesis for drug discovery: Bench to bedside. Accounts of Chemical Research 43 (9) (09/21): 1216-26.

Panzavolta, S., P. Torricelli, B. Bracci, M. Fini, and A. Bigi. 2010. Functionalization of biomimetic calcium phosphate bone cements with alendronate. Journal of Inorganic Biochemistry 104 (10) (10): 1099-106.

Pozzi, Samantha, and Noopur Raje. 2010. Bisphosphonates and atypical femoral fractures. The New England Journal of Medicine 363 (11) (09/09): 1083-4.

Rao, Shobha S., Nitin Budhwar, and Ambreen Ashfaque. 2010. Osteoporosis in men. American Family Physician 82 (5) (09/01): 503-8.

Reid, I. R., G. D. Gamble, P. Mesenbrink, P. Lakatos, and D. M. Black. 2010. Characterization of and risk factors for the acute-phase response after zoledronic acid. The Journal of Clinical Endocrinology and Metabolism 95 (9) (09): 4380-7.

Resnick, J., N. Gupta, J. Wagner, G. Costa, R. J. Cruz J., L. Martin, D. A. Koritsky, et al. 2010. Skeletal integrity and visceral transplantation. American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons 10 (10) (10): 2331-40.

Sambrook, Philip N., Jiang S. Chen, Judy M. Simpson, and Lyn M. March. 2010. Impact of adverse news media on prescriptions for osteoporosis: Effect on fractures and mortality. The Medical Journal of Australia 193 (3) (08/02): 154-6.

Schousboe, J. T., B. E. Dowd, M. L. Davison, and R. L. Kane. 2010. Association of medication attitudes with non-persistence and non-compliance with medication to prevent fractures. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (11) (11): 1899-909.

Sellmeyer, Deborah E. 2010. Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA: The Journal of the American Medical Association 304 (13) (10/06): 1480-4.

Shabestari, Ghasem Omati, Yadollah Soleimani Shayesteh, Arash Khojasteh, Marzieh Alikhasi, Neda Moslemi, Amin Aminian, Reza Masaeli, Behnam Eslami, and Nathaniel S. Treister. 2010. Implant placement in patients with oral bisphosphonate therapy: A case series. Clinical Implant Dentistry and Related Research 12 (3) (09): 175-80.

Shane, Elizabeth, David Burr, Peter R. Ebeling, Bo Abrahamsen, Robert A. Adler, Thomas D. Brown, Angela M. Cheung et al. 2010. Atypical subtroacheteric and diaphyseal femoral fractures: Report of a task force of the American Society for Bone & Mineral Research. Journal of Bone & Mineral Research, e-publication ahead of print, DOI 10.1002/jbmr.253

Shiraki, Masataka, Yasushi Yamazaki, Yumiko Shiraki, Takayuki Hosoi, Naoko Tsugawa, and Toshio Okano. 2010. High level of serum undercarboxylated osteocalcin in patients with incident fractures during bisphosphonate treatment. Journal of Bone and Mineral Metabolism 28 (5) (09): 578-84.

Silverman, Stuart L., Susan M. Ott, and Richard M. Dell. 2010. Bisphosphonates and atypical femoral fractures. The New England Journal of Medicine 363 (11) (09/09): 1083; author reply 1084-5.

Spence, Michele M., Rita L. Hui, James Chan, and Joanne E. Schottinger. 2010. Risk of skeletal-related events in patients with advanced prostate cancer treated with pamidronate or zoledronic acid. The Annals of Pharmacotherapy 44 (9) (09): 1384-8.

Stagi, Stefano, Laura Masi, Serena Capannini, Rolando Cimaz, Giulia Tonini, Marco Matucci-Cerinic, Maurizio de Martino, and Fernanda Falcini. 2010. Cross-sectional and longitudinal evaluation of bone mass in children and young adults with juvenile idiopathic arthritis: The role of bone mass determinants in a large cohort of patients. The Journal of Rheumatology 37 (9) (09): 1935-43.

Ueda, Takeshi, Yusuke Imamura, Atsushi Komaru, Satoshi Fukasawa, Tomokazu Sazuka, Takahito Suyama, Yukio Naya, Naoki Nihei, Tomohiko Ichikawa, and Masayuki Maruoka. 2010. Treatment outcomes of sorafenib for first line or cytokinerefractory advanced renal cell carcinoma in Japanese patients. International Journal of Urology: Official Journal of the Japanese Urological Association 17 (9) (09): 811-5.

Vallet, Sonia, Matthew R. Smith, and Noopur Raje. 2010. Novel bone-targeted strategies in oncology. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 16 (16) (08/15): 4084-93.

Vasudev, Naveen S., and Janet E. Brown. 2010. Medical management of metastatic bone disease. Current Opinion in Supportive and Palliative Care 4 (3) (09): 189-94.

Venkatanarasimha, Nanda, Gemma Miles, and Priya Suresh. 2010. Subtrochanteric femoral insufficiency fractures related to the use of long-term bisphosphonates: A pictorial review. Emergency Radiology 17 (6) (11): 511-5.

Verron, Elise, Olivier Gauthier, Pascal Janvier, Paul Pilet, Julie Lesoeur, Bruno Bujoli, Jerome Guicheux, and Jean-Michel Bouler. 2010. In vivo bone augmentation in an osteoporotic environment using bisphosphonate-loaded calcium deficient apatite. Biomaterials 31 (30) (10): 7776-84.

Werner de Castro, ,G.R., F. S. Neves, de Magalhães Souza Fialho S.C., I. A. Pereira, G. Ribeiro, and A. F. Zimmermann. 2010. Flare-up of hand osteoarthritis caused by zoledronic acid infusion. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 21 (9) (09): 1617-9.

Won, Emily, Lisa Wise-Milestone, Margarete K. Akens, Shane Burch, Albert J. M. Yee, Brian C. Wilson, and Cari M. Whyne. 2010. Beyond bisphosphonates: Photodynamic therapy structurally augments metastatically involved vertebrae and destroys tumor tissue. Breast Cancer Research and Treatment 124 (1) (11): 111-9.

Yamashita, Junro, Laurie K. McCauley, and Catherine Van Poznak. 2010. Updates on osteonecrosis of the jaw. Current Opinion in Supportive and Palliative Care 4 (3) (09): 200-6.

 

Ants, Social Caterpillars, Traffic Jams that Don’t Happen, Audrey Dussutour, Jean-Henri Fabre, & the Continuing Fascination of Insect Behavior

154 years separate the birthdates of   the founder of insect behavioral  studies, Jean-Henri Fabre, and one of his most promising intellectual descendants today, Audrey Dussutour.

Both share certain affinities, apart from their emphasis on the ways and means of interaction in insect societies.

Both are of French ancestry, indeed both come from Southern France, although Dussutour  was initially college-educated at the rather prestigious  Paul Sabatier University in the large city of Toulouse, in Southwestern France, while Fabre was educated in Southeastern France, in Avignon,  a rather small city at what is even now, primarily a schoolteacher’s college, the Ecole Normale de Vauclose, as opposed to the more prestigious university in town.

Fabre had a rather circumscribed career geographically. He taught grade school in  the neighborhood, then moved on to  a small college on the island of Corsica to the south, from which he was driven by bouts of malaria. He finally landed  at a  prep school back  in Avignon, the latter which fired him in 1870,  largely because he admitted girls to his science classes, a practice specifically denounced from the pulpit. (Ironically, he had paid for his early school fees by serving as an altar boy at daily Mass.)

Audrey Dussutour is clearly a beneficiary of  the enlightened policy admitting bright women (as well as bright men) to   education and careers in science, not only in France but around the world. She has  pursued post-doctoral studies not only in France, but in Belgium, Canada, and Australia and collaborated with scientists in the U.S.,  before resuming  her career in France at the Center for Research in Animal Cognition in Toulouse.

Both Fabre and Dussurtour are award-winning scientists, with the primary distinction being that Fabre  had to wait until he was 84 before achieving any academic celebrity, according to an interesting account of Fabre’s life  published as an introduction by Edwin Way Teale,  to a 1957 translation of  Fabre’s selected works.  (cited below)

In 1910, the last of Fabre’s ten-volume series of chatty and often humorous accounts of  insect behavior was published, and ironically, it was the glowing  reviews by prominent literary critics rather than any  raves in scientific journals that made him an “instant celebrity.”  

He had in fact,  been writing about insect behavior for 30 years by then -----an estimated  850, 000 of his words were  in print at the time---- but he was virtually unnoticed and certainly unsponsored by any university or government agency.  

Eventually, realizing that they had a national treasure on their hands in the person of Fabre and in his immense corpus of  charming and highly literate writings on nature,  the French government gave him its  highest award, the Legion of Honor.  

Fabre was granted a federal pension for the last four years of his life,  just in the nick of time,  for he was going blind.  He was also elected to the leading scientific societies and academies in Europe at the time: London, Brussels, Stockholm, Geneva, and St. Petersburg (places by and large that he never got to see.)  

When asked what he wanted to have engraved at the foot of a life-sized statue being erected in his honor, he said “Laboremus!”. This Latin exhortation  has two possible connotations . It can mean: “Let us all diligently work. ”  Or it can mean, “Hey, Stop looking at this statue and get to your place of business!).

Dussutour is only 30 years old, but the quality of her work has already been recognized by no fewer than five financial awards  for her advanced studies.

 Arguably the most notable recent coup was  inclusion of a popularization of her  her work in the Le Monde Prize Collection of University Research, named after France’s most important newspaper, Le Monde.  The paper  sponsors the award, to inform the public about promising work in the arts and  sciences from rising stars in the university system, through essays, written by the researchers, that are deliberately intended to be more accessible to the lay reader.

Fabre would particularly approve of this development as he detested the impersonal turgid style favored by  scholarly journals in his time (and often in ours). He is quoted as saying that academic prose is valued far more for being obscure and capable of being understood only by the few, rather than for being interesting and capable of being understood by the many.

Given the relative youth of her career, it is not too surprising that Dussutour has dealt with a smaller variety  of insects than did Fabre ( who literally wrote about  hundreds of different types) , but what is strikingly similar is a shared emphasis on ants, and to a lesser degree social caterpillars.

Dussutour  deals with many of the many of the same themes as Fabre, but obviously she enjoys and employs  all of the more sophisticated science that has been learned in the interim. (It should be noted that in many respects, Fabre  was a somewhat atavistic  natural historian and   curmudgeon, and had little use for overarching theories, like evolution,  that would have helped him make sense of animal behavior in a larger context.)

Dussutour’s   works  seek the answers  to Fabre-like questions like: How is that ants don’t get into traffic jams? How is it that ants don’t bump into each other when cutting leaves in tight spaces much more than they do when they do leaf-cutting in spacious quarters?  How do ants and social caterpillars make group decisions? What factors   governs decisions about whether or not ants will climb over or around walls? What components of an ant’s diet seem to govern the size of the colony: carbohydrates, fats, proteins?

I suspect that Fabre would be quite pleased in the work of this fellow countrywoman, and highly worthy  intellectual heiress of his scientific tradition.

Tony Stankus [email protected] Life Sciences Librarian & Professor

University of Arkansas Libraries MULN 223-E

365 North McIlroy Avenue

Fayetteville, AR 72701-4002

Voice: 479-409-0021

Fax:  479-575-4592

By & About Fabre

Many of Fabre’s works have been re-issued in translation as collections of essays that all deal with a particular insect or insect relative, even though Fabre himself may not have written all of the reissued essays at the same time or in the same sequence.  Some of these works have been made available from the University Press of the Pacific;  Project Gutenberg Full-Text has scanned in a number as well.

Bicknell, P.F. (1923). The Human Side of Fabre. NY: The Century Company.

Fabre, J.H. (with an Introduction and Interpretive Comments by Edwin Way Teale.) (1957) The Insect World of J. Henri Fabre. NY: Dodd, Mead & Company.

LeGros, G.V. (1913). Fabre, Poet of Science. London: T. Fisher Unwin.

              Selected Works of Audrey Dussutour & A Commentary by Kathryn Knight of the Journal of Experimental Biology

Colasurdo, N., Dussutour, A., & Despland, E. (2007). Do food protein and carbohydrate content influence the pattern of feeding and the tendency to explore of forest tent caterpillars? Journal of Insect Physiology, 53(11), 1160-1168.

Dussutour, A., Beshers, S., Deneubourg, J. L., & Fourcassie, V. (2007). Crowding increases foraging efficiency in the leaf-cutting ant Atta colombica. Insectes Sociaux, 54(2), 158-165.

Dussutour, A., Deneubourg, J. L., Beshers, S., & Fourcassie, V. (2009). Individual and collective problem-solving in a foraging context in the leaf-cutting ant Atta colombica. Animal Cognition, 12(1), 21-30.

Dussutour, A., Deneubourg, J. L., Beshers, S., & Fourcassie, V. (2009). Priority rules govern the organization of traffic on foraging trails under crowding conditions in the leaf-cutting ant, Atta colombica. Journal of Experimental Biology  212, 499-505.

Dussutour, A., Deneubourg, J. L., & Fourcassie, V. (2005a). Amplification of individual preferences in a social context: the case of wall-following in ants. Proceedings of the Royal Society B-Biological Sciences, 272(1564), 705-714.

Dussutour, A., Deneubourg, J. L., & Fourcassie, V. (2005b). Temporal organization of bi-directional traffic in the ant Lasius niger (L.). Journal of Experimental Biology, 208(15), 2903-2912.

Dussutour, A., Fourcassie, V., Helbing, D., & Deneubourg, J. L. (2004). Optimal traffic organization in ants under crowded conditions. Nature, 428(6978), 70-73.

Dussutour, A., Nicolis, S. C., Deneubourg, J. L., & Fourcassie, V. (2006). Collective decisions in ants when foraging under crowded conditions. Behavioral Ecology and Sociobiology, 61(1), 17-30.

Dussutour, A., Nicolis, S. C., Despland, E., & Simpson, S. J. (2008). Individual differences influence collective behaviour in social caterpillars. Animal Behaviour, 76, 5-16.

Dussutour, A., & Simpson, S. J. (2008a). Carbohydrate regulation in relation to colony growth in ants. Journal of Experimental Biology, 211(14), 2224-2232.

Dussutour, A., & Simpson, S. J. (2008b). Description of a simple synthetic diet for studying nutritional responses in ants. Insectes Sociaux, 55(3), 329-333.

Dussutour, A., Simpson, S. J., Despland, E., & Colasurdo, N. (2007). When the group denies individual nutritional wisdom. Animal Behaviour, 74, 931-939.

Knight, K. (2009). Inside JEB:   Ants obey road rules to keep traffic flowing. Journal of Experimental Biology 212, i.

Nicolis, S. C., Despland, E., & Dussutour, A. (2008). Collective decision-making and behavioral polymorphism in group living organisms. Journal of Theoretical Biology, 254(3), 580-586.

Nicolis, S. C., & Dussutour, A. (2008). Self-organization, collective decision making and resource exploitation strategies in social insects. European Physical Journal B, 65(3), 379-385.

Peters, K., Johansson, A., Dussutour, A., & Helbing, D. (2006). Analytical and numerical investigation of ant behavior under crowded conditions. Advances in Complex Systems, 9(4), 337-352.

 

 

It’s Surely Not The Bumps On Your Head; But Differences In Cortical Corrugation Certainly Appear To Be Connected With Autism Spectrum Disorders & Possibly With Higher Intellectual Functioning

Certain misconceptions persist with respect to brain anatomy  but they are being  refuted by more and more evidence from  sophisticated studies in brain surface mapping.  Hilgetag and Barbas (cited below) represent one of many intriguing new looks at the issue, and of the many papers cited below, probably provide for the best exposition for dedicated lay readers with some science background.  

Size Doesn’t Matter (All that Much)

The overall size and weight of the brain, beyond the extreme of microencephaly, are not a particularly good predictors of intellectual capability. Einsteins’ brain is said to have been about 10% smaller than average, and this clearly did not hold him back any.

Brain Weight Differences Between Genders Are Real, But Claims of Serious Cognitive Advantages by Either Sex Because of This Are Illusory

Likewise, it is true that the brains of men are   predictably heavier than the brains of women, but there is a spectrum of crossover, and I can clearly imagine many men with ostensibly heavier brains who are less intelligent than any number of women with presumably lighter brains.

Computer imaging studies can correctly identify the gender of the brain through geometric scaling and weight information about 85% of the time, but do not appear to be particularly good yet at predicting intelligence per se in either or both genders, given the absence of gross abnormalities.

 White Matter is Vastly More Abundant in the Brain, But Grey Matter Matters More

White matter easily makes up more than 90% of your brain by volume, but it is the thin coat of grey matter commonly called the cerebral cortex, that seems to account for virtually all of the thinking, remembering, and even a  good deal of our emoting.

Relative Cortical Thickness Does Matter, Particularly in Frontal Regions Versus The Rest Of The Brain

Cortical thickness presents us with a paradox. The general thickness of the cerebral cortex correlates pretty well with intelligence across most ages, but especially so  in children.

Yet virtually all cerebral cortexes tend to thin with age, and yet, as adults we do not grow less intelligent (despite what our children have to say about it). 

But it turns out that having a noticeably thicker cortex as an adult  in areas of the brain that are associated with higher intelligence  relative to the cortical thickness in other areas of the brain of the same subject seems to be a better predictor of adult intelligence, although this finding has not been confirmed with a great many subjects (perhaps 200 thus far)  yet.

For what it’s worth, given the general dictum that claims of superiority based on gender differences in brain anatomy are a tricky proposition, as they age, women tend  better to preserve relative frontal cortical thickness than men as they age.

Differences in the Degree & Pattern of Brain Folding May Be Predictive of Some Abilities

In general, it appears to be better to have a greater degree of folding in your temporo-occipital lobes, and in a study of 65 healthy adult subjects, there appeared to be a pretty straightforward relationship in IQ with increased corrugation. 

There is also some  evidence that the relative number of folds, rather than the relative depth of the folds is also a better predictor of IQ. 

Indeed, there is an increasing amount of evidence that  suggests that brains that exhibit a kind of fractal pattern of  developing many branching folds seem to allow for  higher cognitive function in their owners.

What is particularly intriguing here is that remapping the same brain at different ages, and comparing results with increasing years of education  indicates that  learning new subject material and having culturally enriching experiences fosters  just that sort of positive anatomical sophistication. It appears that we can improve on Mother Nature, because the brain exhibits plasticity in its folding patterns over time, particularly in youth.

Not All Folds Are Equally Good & the Timing of the Fold-Making Seems More Important Than Formerly Thought

It appears that autistics, particularly young autistic children,  actually have what might be termed too many folds too early to handle them.  The theory is that the overabundance and perhaps the excess of proximity of these folds at a time when the brain’s filtering processes are not ready to handle them, causes a kind of cognitive overload, sort of like too many radio transmitters broadcasting with too similar a frequency making it hard to tune one’s radio to hear any one program clearly (in the pre-HD era, at any rate).

There  is already pretty good evidence that scans and comparisons of the degree of the severity of certain folding abnormalities can predict and sort out who are the  low-functioning autistics, vs. the high-functioning autistics, vs. Asperger’s Syndrome patients, in the sense that well-vetted interview and test-taking techniques long used to make clinical diagnoses of severity of autism spectrum disorders correlate very well with  imaging results.

There is less clear, but suggestive data that schizophrenics and  bipolar patients tends to have similar cortical folding abnormalities, but the correlation of degree of severity of illness with pattern or depth, and certainly  a theory of causation based on folds, are not there, at least yet. 

Is there Any Hope for Curatively Refolding the Cortex?

At least one paper suggests that the brains of schizophrenics are too plastic, meaning that they are too likely to reshape their folds  or do so too quickly or too often. However, even among those with some of the worse brain disorders, there are moments of relative stability, even among adolescents, and some have theorized that the cortex can then be more subtly and selectively refolded. The method is not likely to be some sort of surgery on the folds.

Rather it might just be something as utterly repetitive but potentially brain reshaping as playing video games, thousands and thousands of times. As Gary Stix notes in a commentary in Scientific American (cited below) “Grand Theft Auto IV or Medal of Honor may retrain the brain in ways its developers never imagined.”

So maybe our teenagers are smarter than us, at least about the potential for good in their endless fascination and preoccupation with even the most violent of action-packed video games.

But, that’s still an unproven theory, and I would not say sufficiently evidence-based that it should change your requests that they do their math homework, at least first.

Tony Stankus, [email protected] Life Sciences Librarian & Professor

University of Arkansas Libraries MULN 223 –E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-409-0021

Fax: 479-575-4592

 

Acosta, M.T. & Pearl, P.L. (2004). Imaging data in autism: From structure to malfunction. Seminars in Pediatric Neurology 11 (3), 205-213.

Anticevic, A., Dierker, D. L., Gillespie, S. K., Repovs, G., Csernansky, J. G., Van Essen, D. C., et al. (2008). Comparing surface-based and volume-based analyses of functional neuroimaging data in patients with schizophrenia. NeuroImage, 41(3), 835-848.

Awate, S.P., Win, L., Yushkevich, P., Schultz, R.T. & Gee, J.C. (2008). 3-D cerebral cortical morphometry in autism: Increased folding in children and adolescents in frontal, parietal, and temporal lobes.  Medical Image Computing & Computer-Assisted Intervention, 11 (part 1), 559-567.

Cykowski, M. D., Kochunov, P. V., Ingham, R. J., Ingham, J. C., Mangin, J. F., Riviere, D., et al. (2008). Perisylvian sulcal morphology and cerebral asymmetry patterns in adults who stutter. Cerebral Cortex, 18(3), 571-583.

Dubois, J., Benders, M., Borradori-Tolsa, C., Cachia, A., Lazeyras, F., Ha-Vinh Leuchter, R., et al. (2008). Primary cortical folding in the human newborn: An early marker of later functional development. Brain, 131(Pt 8), 2028-2041.

Dubois, J., Benders, M., Cachia, A., Lazeyras, F., Ha-Vinh Leuchter, R., Sizonenko, S. V., et al. (2008). Mapping the early cortical folding process in the preterm newborn brain. Cerebral Cortex, 18(6), 1444-1454.

Duchesnay, E., Cachia, A., Roche, A., Riviere, D., Cointepas, Y., Papadopoulos-Orfanos, D., et al. (2007). Classification based on cortical folding patterns. IEEE Transactions on Medical Imaging, 26(4), 553-565.

Fischl, B., Rajendran, N., Busa, E., Augustinack, J., Hinds, O., Yeo, B. T., et al. (2008). Cortical folding patterns and predicting cytoarchitecture. Cerebral Cortex, 18(8), 1973-1980.

Fornito, A. Yucel, M., Wood, S., Stuart, G.W., Buchanan, J.A., Proffitt, T., Anderson, Y.,  Velakoulis, D. & Panatelis, C. (2004). Individual differences in anterior cingulated/paracingulate morphology are related to executive functions in healthy males. Cerebral Cortex 14 (4), 424-431.

Fornito, A., Malhi, G. S., Lagopoulos, J., Ivanovski, B., Wood, S. J., Saling, M. M., et al. (2008). Anatomical abnormalities of the anterior cingulate and paracingulate cortex in patients with bipolar I disorder. Psychiatry Research, 162(2), 123-132.

Hilgetag, C.C., & Barbas, H. (2009). Sculpting the brain. Scientific American 300 (2), (February), 66-71.

Im, K. Lee, J.M., Yoon, U., Shin, Y.W., Hong, S.B., Kim, I.Y. Kwon, J.S., & Kim, S.I. (2006). Fractal dimensions in human cortical surface: Multiple regressive analysis with cortical thickness, sulcal depth, and folding area. Human Brain Mapping 27 (12): 994-1003.

Lohmann, G., von Cramon, D. Y., & Colchester, A. C. (2008). Deep sulcal landmarks provide an organizing framework for human cortical folding. Cerebral Cortex, 18(6), 1415-1420.

Luders, E., Nar, K.L., Bilder, R.M., Szesko, P.R., Gurbani, M.N., Hamilton, L., Toga, A.W. & Gaser, C. (2008). Mapping the relationship between cortical convolution and intelligence: Effects of gender. Cerebral Cortex 18(9), 2019-2026.

Nordahl, C.W., Dierker, D., Mostafavi, I., Schumann, C.M., Rivera, S.M., Amaral, D.G. & Van Essen, D.C. (2007). Cortical folding abnormalities in autism revealed by surface-based morphometry.  Journal of Neuroscience 27 (43): 11725-11735.

Postelnicu, G., Zollei, L., Desikan, R., & Fischl, B. (2007). Geometry driven volumetric registration. Information Processing in Medical Imaging  20, 675-686.

Rilea, S. L. (2008). A lateralization of function approach to sex differences in spatial ability: A reexamination. Brain and Cognition, 67(2), 168-182.

Rodriguez-Carranza, C., Mukherjee, P., Vigneron, D., Barkovich, J. & Studholme, C. (2006). Medical Image Computing & Computer-Assisted Intervention 9 (part 2), 201-208.

Sandu, A. L., Rasmussen, I. A.,Jr, Lundervold, A., Kreuder, F., Neckelmann, G., Hugdahl, K., et al. (2008). Fractal dimension analysis of MR images reveals grey matter structure irregularities in schizophrenia. Computerized Medical Imaging and Graphics, 32(2), 150-158.

Shaw, P. (2007).  Intelligence and the developing human brain. BioEssays 29 (10), 962-973.

Shaw, P., Greenstein, D., Lerch, J., Clasen, L., Lenroot, R., Gogtay, N., Evans, A., Rapoport, J. & Giedd, J. (2006). Intellectual ability and cortical development in children and adolescents. Nature 440 (7084), 676-679.

Sowell, E.R., Petersen, B.S., Kan, E., Woods, R.P., Yoshii, J. Banmsai, R., Xu, D., Zhu, H. Thompson, PM,  & Toga, A.W. (2007).  Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age. Cerebral Cortex  17 (7), 1550-1560.

Stanfield, A. C., Moorhead, T. W., Harris, J. M., Owens, D. G., Lawrie, S. M., & Johnstone, E. C. (2008). Increased right prefrontal cortical folding in adolescents at risk of schizophrenia for cognitive reasons. Biological Psychiatry, 63(1), 80-85.

Stix, G. (2009). Neurobiology. Childhood recovered: “Lazy eye” studies show how adult brains can be rewired back to youth. Scientific American 300 (2), (February), 27-28.

Takahashi, T., Yung, A. R., Yucel, M., Wood, S. J., Phillips, L. J., Harding, I. H., et al. (2008). Prevalence of large cavum septi pellucidi in ultra high-risk individuals and patients with psychotic disorders. Schizophrenia Research, 105(1-3), 236-244.

Toro, R., Perron, M., Pike, B., Richer, L., Veillette, S., Pausova, Z., et al. (2008). Brain size and folding of the human cerebral cortex. Cerebral Cortex, 18(10), 2352-2357.

Tsujimoto, S. (2008). The prefrontal cortex: Functional neural development during early childhood.  The Neuroscientist 14, (4), August), 345-358.

Voets, N. L., Hough, M. G., Douaud, G., Matthews, P. M., James, A., Winmill, L., et al. (2008). Evidence for abnormalities of cortical development in adolescent-onset schizophrenia. NeuroImage, 43(4), 665-675.

Wisco, J. J., Kuperberg, G., Manoach, D., Quinn, B. T., Busa, E., Fischl, B., et al. (2007). Abnormal cortical folding patterns within Broca's area in schizophrenia: Evidence from structural MRI. Schizophrenia Research, 94(1-3), 317-327.

Is Fear Of Being Attacked In The Animal Kingdom Inherited Or Learned? If Forgotten, Can It Be Re-Learned? Joel Berger’s Book, “The Better To Eat You With” Offers Some Clues

Indiana Jones is a wildly popular daring-do movie-matinee adventurer,   known to millions,  but Joel Berger of the University of Montana and the Wildlife Conservation Society is  perhaps braver (and   crazier) , but very real, and ought to be better known by biomedical and life science librarians and their readers.

In his book, The Better to Eat You With: Fear in the Animal World (The University of Chicago Press, 2008. ISBN: 13: 9878-0-226-04363-0), uses exceptional ingenuity to find scenarios and develop tactics to test hypotheses about how prey animals, most commonly moose, elk, and buffalos come to fear and flee from (and occasionally to fight with) predators: mostly wolves, but also grizzly and black bears, and the occasional mountain lion, Siberian tiger or snow leopard.

Interviewing is pretty much out, the fictional Bullwinkle’s talkativeness aside, so observation is pretty much the only way to figure it out, but it is the behavioral and environmental manipulations that Berger uses that helps him create something like a laboratory of experimental animal psychology wherever he goes.

Here are some of the situations he explores in his book.

How can you tell when a prey animal is concerned about an approaching predator? What are good measurable indicators of initial predator awareness? Watchful waiting? Intention to flee?

If you have had a cat, you might have guessed that pilo- erection (the hair-raising of many mammals when being threatened or threatening others) is certainly one clue, but is it quantifiable?  And at what distance does such an observation become unreliable?  

Berger suggests that the time for some animals, particularly large hoofed game, the  which point the animal interrupts its browsing, and the duration of the interruption, and any repeated sequences of the interruptions,  are things that can be not only counted but timed to develop data points.

Prey animals that interrupt sooner, interrupt longer, and interrupt more often, have probably learned to be more wary, or were given a genetic endowment that favors wariness. He even offers a scenario how this might be tested, and the issue of learning  to fear versus inherited fear.

For this test, we need (and Berger finds)  three populations of moose, for example. 

1.     Those prey animals who have lived with wolves or bear or cougars around all their lives (e.g. moose in parts of the Canadian wilderness where predators were not extirpated). They should be the measurably the wariest, although sorting out whether or not learning or heredity is dominant would still be difficult.

2.     Those  prey animals that live in areas where there have never been predators, for example, those who live on remote islands that never had predators. They should be measurably  the least wary, although if they are unexpectedly very wary, a score in favor of inherited fear might be better made.

3.     Those prey animals who live in an area where predators are being re-introduced after an absence of many generations of prey animals. If the prey are very wary, right from the start of the reintroduction,   such fear is unlikely to be a learned behavior. It is likely to be inherited instinct. But , if the animals are initially clueless, and suffer great losses to predation, but then  learn to cope by being wary, fleeing sooner, or getting more combative, then we might say that fear is learnable and learned.

In numerous studies detailed colorfully in the book, Berger tends to come down on the side of fear being primarily learned.

He bases this on the early experiences of naïve prey in national parks where wolves are re-introduced. Large mother moose who could flee with their calves or fight on behalf of their calves, often lose a calf on their first encounter ever with a predator.

But the lesson is often learned by next calving season. Prey are by no means uneducable. In fact, in cases where their prey is more social (elk are gregarious more often than  moose and apparently can learn from observation or some form of communication) it appears that learning to be wary and flee sooner can somehow be transmitted to elk mothers who have not personally lost calves.

Seeing a wolf or a bear or a cougar attack a prey animal is not always a practical way to judge alertness and fear responses, quite possibly because you cannot count on either predator or prey showing up exactly at the same time, whenever you are ready  to observe them.

So Berger develops a number of proxy situations. He asks himself: Will moose in areas that have long had abundant predators predictably react more quickly to a recording of a wolf howl, than will totally naïve moose? (The answer is dramatically YES….for naïve moose often do not react at all). But will the time to demonstrate an alert response also be shown to decrease in animals that used to be naïve, but have had a new if sad experience with predators? (The answer is also yes.) This last suggest learning once again.

A trick question might be if it is just the noise that matters. But it turns out that recording of loud howler monkeys does not get much of a rise, despite equal blaring.

One surprise, however, is that the roar of the African lion uniformly causes an alert state of fear even in animals which have never seen a lion in a thousand years or recent history. Berger suggests that this anomaly is perhaps best explained by the fact that some fear responses are genetically preserved, perhaps because they were uniformly lethal for those who did not inherit that particular type of fearfulness.

Berger points out the fact that throughout pre-historic North America, a variety of giant lion-like predators, much larger than mountain lions, and presumably with vocalizations similar to the African lion, were clearly present.  This can be seen from fossil findings,  from the retrieval of bones from site like the LaBrea tar pits, and from human-made cave paintings or other artifacts.

In one of his most interesting speculations, he suggests that the timing of the of Asiatic migration to North America might have been  influenced by more than just the periods at which a land bridge existed or water-craft were invented.

He suggests it might have been held up until those Asiatic hunter peoples developed their own fear-and-experience-based ways of fending off predators in order for themselves to become predators on the large animal prey of the time (e.g. mammoths) more plentiful in the New World.

Berger also demonstrate that there is some evidence that prey animals can associate, and react with fear, to  the sounds of scavengers (like ravens or eagles or vultures)  with the presence  of the predators that initially killed the prey. In other words, some of them realize and internalized the notion that the  Lords of Leftovers had to be preceded by the Princes of the Prime cuts. If the one were around, the other could not be far away.

Of course, there are other pungent parts of the book, such as Berger’s expertise in tossing snowballs of lion’s urine or  bear crap in order to detect if olfactory cues also factor into different levels of awareness.

Do naïve prey ignore or dismiss odiferous signs of imminent danger (pretty much); do those raised constantly with predators respond more reliably and appropriately (yup!), and can a change in sensory awareness and signal processing be observed in animals transitioning to a new world that now includes predators? (it seems so.)

All along the way, are other interesting nuggets of animal behavior information, including the role of the influence of leaders.

 For example, there are pods where it appears that the lead whale learns to pick fish off of commercial fishing lines, and the rest of the group learns from him. However, when the lead whale dies, the pod simply forgets this new skill.

And clearly there are differences of intelligence and personality even among animals within the same species and pack.

For example,  leading life sciences librarians with  an interest in animal learning and the transmission of fear and flight behaviors, and a few bucks, will demonstrate their superior intelligence by getting this book as soon as they sense its importance!

The others, well, they  may could fall prey to critical  faculty customers who want to know why this valuable resouce was not already in place.

Tony Stankus [email protected] Life Sciences Librarian & Professor

University of Arkansas Libraries MUULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-575-0021

Fax: 479-575-4592