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Turning on hormone tap could aid osteoporosis fight
July 16, 2008A potential new drug that 'opens the taps' for the release of useful hormones could stimulate new bone growth - and may eventually bring relief to osteoporosis sufferers.
The exciting potential of so-called negative allosteric modulators will be put under the microscope at a special symposium at The Federation of European Pharmacological Societies (EPHAR) 2008 Congress at The University of Manchester, UK, today (Wednesday, July 16).
European pharmacologists meeting in Manchester will present work that focuses on the stimulation of parathyroids - tiny glands located above the thyroids that control the release of the parathyroid (PTH) hormone into the bloodstream.
When the concentration of calcium is too low in the blood's plasma, PTH is released and acts on various tissues to increase the level of calcium in the blood. This calcium then activates the calcium sensing receptor on the parathyroid cell, which then reduces PTH release.
The first POSITIVE allosteric modulator was recently introduced into clinical practice for treating patients displaying high levels of PTH in the plasma - such as those with chronic kidney disease on dialysis and those displaying hypercalcaemia with parathyroid cancer. It mimics the effect of calcium on the receptor and so reduces PTH release.
But now attention is switching to NEGATIVE allosteric modulators, which have been shown in pre-clinical trials to block the effect of calcium on the parathyroid cell and thus increase the release of PTH in the serum.
"Daily administration of a negative allosteric modulator of the calcium sensing receptor should promote a sustained increase of PTH in such a way that it will stimulate new bone formation," said symposium organiser Martial Ruat, a neuropharmacologist at the government funded Centre National de la Recherche Scientifique in France.
"Now clinical trials will have to demonstrate the effectiveness and suitability of negative allosteric modulators for treating osteoporosis in humans."
While pharmacologists are excited and encouraged by results so far, Dr Ruat says it will be at least another eight to 10 years before negative allosteric modulators are passed for use in patients "Osteoporosis is a complex disease and the timescale might be rather long," says Dr Ruat, who is himself carrying out research to learn more about the potential benefits of both negative and positive allosteric modulators.
He added: "The calcium sensing receptor is also found in the kidney, the intestine, in some vascular and bone cells and also in the brain. We still need to identify the roles of this receptor in these tissues before being able to specify novel applications of these drugs."
Negative and positive allosteric modulators are also being studied by European pharmacologists with a view to identifying the functions of calcium sensing receptors in the control of blood pressure.
University of Manchester
When the concentration of calcium is too low in the blood's plasma, PTH is released and acts on various tissues to increase the level of calcium in the blood. This calcium then activates the calcium sensing receptor on the parathyroid cell, which then reduces PTH release.
The first POSITIVE allosteric modulator was recently introduced into clinical practice for treating patients displaying high levels of PTH in the plasma - such as those with chronic kidney disease on dialysis and those displaying hypercalcaemia with parathyroid cancer. It mimics the effect of calcium on the receptor and so reduces PTH release.
But now attention is switching to NEGATIVE allosteric modulators, which have been shown in pre-clinical trials to block the effect of calcium on the parathyroid cell and thus increase the release of PTH in the serum.
"Daily administration of a negative allosteric modulator of the calcium sensing receptor should promote a sustained increase of PTH in such a way that it will stimulate new bone formation," said symposium organiser Martial Ruat, a neuropharmacologist at the government funded Centre National de la Recherche Scientifique in France.
"Now clinical trials will have to demonstrate the effectiveness and suitability of negative allosteric modulators for treating osteoporosis in humans."
While pharmacologists are excited and encouraged by results so far, Dr Ruat says it will be at least another eight to 10 years before negative allosteric modulators are passed for use in patients "Osteoporosis is a complex disease and the timescale might be rather long," says Dr Ruat, who is himself carrying out research to learn more about the potential benefits of both negative and positive allosteric modulators.
He added: "The calcium sensing receptor is also found in the kidney, the intestine, in some vascular and bone cells and also in the brain. We still need to identify the roles of this receptor in these tissues before being able to specify novel applications of these drugs."
Negative and positive allosteric modulators are also being studied by European pharmacologists with a view to identifying the functions of calcium sensing receptors in the control of blood pressure.
University of Manchester
Osteoporosis Current Events and Osteoporosis News RSSNation's hip fracture rate could drop 25 percent with aggressive osteoporosis prevention
Aggressively managing patients at risk for osteoporosis could reduce the hip fracture rate in the United States by 25 percent, according to a Kaiser Permanente study published in the November issue of the Journal of Bone & Joint Surgery.
Fabled 'vegetable lamb' plant contains potential treatment for osteoporosis
The "vegetable lamb" plant - once believed to bear fruit that ripened into a living baby sheep - produces substances that show promise in laboratory experiments as new treatments for osteoporosis, the bone-thinning disease.
New data: Hospital imaging centers poised to pull back, hitting patients hardest in rural areas
Survivors and patients with cancers and heart disease, along with patient advocate organizations and physicians, today urged policymakers to enhance early diagnosis of deadly diseases by preserving access to advanced imaging, such as MRI and CT scans, in final health care reform legislation.
New approach for growing bone comes from Duke preclinical research
The natural cycle of building bone to maintain skeletal strength and then breaking it down for the body's calcium needs is delicately balanced, but diseases like osteoporosis break down too much bone without adequate bone replacement, leading to bone fractures.
New link found between osteoporosis and coeliac disease
People with coeliac disease may develop osteoporosis because their immune system attacks their bone tissue, a new study has shown.
National report shines light on lupus 50-year treatment drought
Today, The Lewin Group, a national health care consulting firm, issued recommendations on ways to overcome the barriers that have obstructed lupus drug development resulting in no new drug approval for this disease in more than 50 years - since the Eisenhower Administration.
Breast milk should be drunk at the same time of day that it is expressed
The levels of the components in breast milk change every 24 hours in response to the needs of the baby. A new study published in the journal Nutritional Neuroscience shows, for example, how this milk could help newborn babies to sleep.
Wrist fracture patients less likely to be evaluated for osteoporosis
A study published in the October 2009 issue of the Journal of Bone and Joint Surgery suggests a disconnect between the way wrist-fracture patients and those with a spine or hip fracture are managed and evaluated.
Researchers identify new brain pathway for regulating weight and bone mass
Contrary to the prevailing view, the hormone leptin, which is critical for normal food intake and metabolism, appears to regulate bone mass and suppress appetite by acting mainly through serotonin pathways in the brain.
Experimental approach may reverse rheumatoid arthritis and osteoporosis
Researchers have identified a mechanism that may keep a well known signaling molecule from eroding bone and inflaming joints, according to an early study published online today in the Journal of Clinical Investigation.
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