Medical / Osteoporosis / February 14, 2012

Prescription Drugs that Cause Osteoporosis: Here’s What You Can Do to Protect Yourself

You May Be Taking One of the Commonly Prescribed Drugs that Cause Osteoporosis: Here’s What You Can Do to Protect Yourself

Did you know that drugs commonly prescribed to treat epilepsy, anxiety, insomnia, depression, schizophrenia and even restless leg syndrome cause osteoporosis?

I’ve just learned a great deal more about this, inspired by Julie, who wrote me that, although only age 50, she has severe osteoporosis.  Her doctors say her bones are “like twigs.” In the last 2 ½ years, she has suffered fractures of both her hip and leg. When I wrote back in hopes of helping her figure out why her bones have become so brittle at such a young age, she replied she already knew why:

“I have had epilepsy since I was 6 months old. All epilepsy drugs cause a deficiency in calcium and vitamin D. This is a known fact, and I should have had regular blood tests throughout my life to monitor this, and, hopefully prevent the osteoporosis. This, of course, was never done, and even now they don’t do it, so I have given up asking for it to be done. They only did a test to check bone density a few years ago. By that time, I already had the condition, and it was just a matter of time before I had the first fracture, a couple of years later.”

Needless to say, I was very distressed that her doctors did not monitor the effects on her bones of the drugs they prescribed to manage her epilepsy. Her excessive bone loss could have been prevented!

I’m writing here now in hopes that, together, we can help protect others with epilepsy from developing osteoporosis. If you must take anticonvulsants, I want you to know that osteoporosis does not need to be in your future! If you have epilepsy, there is much you can do to safely, effectively and naturally protect your bones – and, should you have already developed osteoporosis, to restore your bones’ health.

In Your Bones, I wrote (p. 106 and following) about the fact that anticonvulsant drugs used to manage epilepsy (e.g, phenytoin [trade name, Dilantin]; primidone, phenobarbital [trade name, Luminal], valproic acid [trade name, Depacon]) greatly increase risk for osteoporosis. These drugs interfere with vitamin D absorption & metabolism, may cause deficiency of folate and/or vitamin B6, and reduce blood levels of vitamin K – all of which play important roles in bone health.

Julie lives in Europe, where the latest position statement issued by the European Menopause & Andropause Society (EMAS), January 11, 2012, notes that 50-70% of all Europeans are deficient in vitamin D. Since her needs for this nutrient critical for bone health are increased by the anticonvulsants required to manage her epilepsy, it’s highly likely that Julie needs even more than the 4,000 IU/day of vitamin D now recommended by the lead author of the EMAS position paper, Dr. Pérez-López, for postmenopausal women with any of the following risk factors for vitamin D insufficiency: obesity, dark skin, intestinal malabsorption, or residing close to the North or South poles.[1]

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Drugs Used to Manage Anxiety, Depression, Schizophrenia & Restless Leg Syndrome Also Cause Bone Loss

While checking for the most recently published medical journal articles on the bone-depleting effects of the drugs used to manage epilepsy, I discovered that the benzodiazepines, (e.g., Valium, Xanax, Librium, Halcion—and many others[2]), another class of drugs frequently prescribed to treat not just epilepsy, but also anxiety, insomnia, depression, schizophrenia and restless leg syndrome, also cause significant bone loss. Many recent studies confirm this.

One study conducted in Spain, for which results were published in 208, assessed risk factors for osteoporosis and fractures in a large sample of women – 4,960 postmenopausal women aged 50 to 65 years, who were being seen at 96 different primary care facilities across the country. The two top risk factors identified for osteoporosis were low intake of calcium and benzodiazepine use.[3]

Benzodiazepine Drugs Cause Bone Loss

The latest medical journal review articles (reviews are papers that summarize the results of many studies) are now warning physicians that the entire class of benzodiazepines (and as noted above see [2], there are numerous drugs in this group) cause chronic elevation of the hormone, prolactin. These drugs bind to and block off dopamine receptors in the hypothalamus (an area in the brain). By this action, the benzodiazepines prevent dopamine, another important neurotransmitter, from being secreted. Unfortunately, shutting down the secretion of dopamine causes prolactin levels to rise because dopamine is what turns off the pituitary gland’s secretion of prolactin.

How does having chronically high levels of prolactin cause bone loss?

High prolactin levels (a condition referred to in the medical literature as “hyperprolactinaemia”), suppress the activity of the hypothalamic-pituitary-gonadal axis. This triad of endocrine glands interacts and secretes a number of hormones involved with reproduction. The hypothalamus produces gonadotropin-releasing hormone (GnRH). The anterior portion of the pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the gonads (ovaries in women, testes in men) produce estrogen and testosterone, respectively.

More accurately, the pituitary’s secretion of FSH and LH are what signal the gonads to produce estrogen, progesterone, and testosterone. Since estrogen and progesterone play very important roles in maintaining healthy bones in women, inhibiting their production by inhibiting that of FSH and LH causes bone loss. Estrogen prevents excessive activation of osteoclasts (the specialized cells that break down old bone), while progesterone activates osteoblasts (specialized cells involved in building new bone). This is why the drop off in the production of these hormones that occurs with menopause contributes to bone loss. Even in men, estrogen is essential for bone health. Men convert a small, but very necessary amount, of testosterone into an estrogen that plays a critical role in maintaining men’s bones, which is why drugs that disrupt testosterone production cause bone loss in men.

Drugs Commonly Used to Manage Anxiety and Depression Cause Bone Loss

A study, published February 2011, which involved more than 27,000 postmenopausal women in Canada, found that selective serotonin reuptake inhibitors (SSRIs, e.g.,Prozac, Paxil, Zoloft and many others[4]) increased risk for osteoporosis by 46%, atypical antipsychotics (tranquilizers, also called 2nd generation antipsychotics, e.g., trade names Zyprexa, Risperdal, Seroquel, Geoden, Zeldox, Ablify [5]) increased risk by 55%, and benzodiazepines (e.g., Diazepam, Xanax, Paxil, Librium, Valium, and many others; SSRIs are among the benzodiazepines) increased risk by 17%. [6]

Another very large study conducted in Spain—this one included more than 63,000 subjects—found SSRIs to be associated with the highest adjusted odds of osteoporotic fractures –a 45% increased risk. Monoamine oxidase inhibitor antidepressants (MAOIs are less frequently prescribed these days; the most commonly used MAOI is Ensam, a transdermal patch of the MAOI, selegiline) increased risk for osteoporosis 15%, and benzodiazepines increased risk by 10%. A dose-effect relationship was seen with SSRIs and benzodiazepines – the longer any of these drugs was used, the greater the increase in risk for osteoporosis. In contrast, lithium, which is prescribed to manage bipolar disorder, was associated with a 37% lower risk for fracture risk. [7]

SSRIs are very commonly prescribed antidepressants – e.g., Prozac, Valium. These drugs are supposed to just increase brain levels of the neurotransmitter, serotonin, by preventing its reuptake by the neurons that secrete it. However, it has recently been revealed that SSRIs also inhibit dopamine production and neurotransmission[8] – which, as explained above, causes high prolactin levels, endocrine dysfunction and bone loss.

Researchers have now reported very high rates of osteoporosis and osteopenia in people taking long-term psychoactive drugs (e.g., anticonvulsants, benzodiazepines), and the higher the dose and longer the drugs were taken, the greater the bone loss.

Young Caucasian women have been found to be especially vulnerable to developing high prolactin levels (hyperprolactinaemia), with the resulting inhibition of estrogen and progesterone production, and bone loss. Younger women taking any of these drugs and experiencing menstrual problems (an indication that the drug is disrupting normal function of the hypothalamic-pituitary-gonadal axis) should immediately alert their doctors and request tests to evaluate their prolactin levels and BMD.

Ideally, work with a physician knowledgeable about integrative, holistic and/or naturopathic medicine, who can help you identify the underlying causes of your health issues and help you restore your health using effective and safe, natural means.

You do not want a prescription for yet another drug, like a bisphosphonate (e.g., Fosamax, Boniva, Reclast), or one of the other drugs I am now seeing being advocated since women are aware of bisphosphonates’ adverse effects and are refusing to take them. The two latest drugs the pharmaceutical companies are telling doctors to prescribe are denosumab (trade name, Prolia) and teriparatide (trade name, Forteo), neither of which will help you restore normal bone rebuilding and both of which can have significant adverse side effects.

In the Resources section of Your Bones, I’ve provided a full list of medical organizations you can contact to help you find physicians in your area who can help you restore your health naturally. I cannot list them all here, but three such national groups are the American Holistic Medical Association (www.holisticmedicine.org), the American Association of Naturopathic Physicians (www.naturopathic.org) and the Institute for Functional Medicine (www.functionalmedicine.org)

If you must take a psychoactive medication, please discuss which drug might be least harmful with your doctor. Some of these drugs have a lesser antagonizing effect on dopamine receptors in the brain. Others are potent dopamine receptor antagonists, and it is by antagonizing dopamine receptors that antipsychotic drugs cause hyperprolactinaemia—and thus osteoporosis. Conventional psychoactive drugs all cause hyperprolactinemia, but a few of the so-called “atypical” psychoactive drugs, supposedly, do not. I’ve provided references [9],[10] for the latest studies discussing this in the peer-reviewed medical literature. Share these with your doctor and ask for help finding the psychoactive drug with the lowest prolactin-raising profile.

If you are taking one of these drugs because you suffer from depression, you could also ask your physician about switching to a tricyclic antidepressant (Again, working with a physician who can help you understand and naturally correct the underlying causes of your health issues is your best option. Also, once again, there are way too many of these drugs to list here; a link to a full listing is provided below in reference [11]). Tricyclic antidepressants do not appear to promote bone loss and, in one study, were associated with 43% lower risk for osteoporosis.[5]

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The Good News: You Can Halt and Even Reverse Antipsychotic-Drug Associated Bone Loss – Naturally

The good news for anyone with epilepsy – or the numerous other conditions for which psychoactive drugs are prescribed, e.g., depression, insomnia, schizophrenia, restless leg syndrome – is that even if you must continue to take these drugs, you absolutely can combat their side-effects and restore your bones’ health, naturally. Findings in the research studies show that “active management” of bone loss in those with psychoactive drug-associated osteopenia / osteoporosis “can halt or even reverse this process.”[8]

Obviously, intelligent “active management” does not mean taking yet another drug, like a bisphosphonate, with even more bone- and health-destroying side effects!  Intelligent “active management” means supplying your bones with all the nutrients they require to remodel, rebuild and maintain healthful structure and function. It also means correcting or avoiding, when at all possible, the many other factors in our modern lifestyle that promote bone loss, which I discuss in detail in Your Bones. While I cannot recount the entire assortment of these for you here, I can give you what I consider to be some key recommendations regarding nutrients essential for bone health.

Take a highly bio-available form of calcium

As I discuss in Your Bones, several different forms of calcium are used in supplements, but they are not equally well absorbed or utilized by our bodies. YOU need the most effectively absorbed and able-to-be-utilized-by-your-bones form of calcium. So do I, which is why I now take AlgaeCal. I learned about AlgaeCal after Your Bones was published, too late to include it in the first edition of the book, but it will definitely be in the second edition! Other calcium supplements are derived from inedible rock. AlgaeCal is derived from sea-algae, i.e., from living plants that draw calcium and 70 other minerals from sea water and convert them into nourishing form. Thus, AlgaeCal’s plant-digested calcium is optimally bio-available. And many of those other minerals naturally present in AlgaeCal (also in highly bio-available form) play important roles in building bone. Plus, research studies using AlgaeCal prove its effectiveness – a very unusual situation in the natural products industry where, unlike drugs, products cannot be patented, so very few companies spend the money on research to see if their products are truly helpful.

Ensure you are getting vitamin D in an amount sufficient to meet YOUR specific needs

You will need more vitamin D than the average person to get your levels up where they should be. Fortunately, this is easy to do. You just need to have your vitamin D levels checked (a simple blood test to determine your levels of 25(OH)D—a form of vitamin D found in the blood that is the best indicator of overall body status—and then supplement with the amount of vitamin D that YOU need to bring your blood levels of 25(OH)D into optimal range, which is 60-80 ng/mL. For most people (even those whose bones are not compromised by psychoactive drugs), this will mean supplementing with 5,000 IU of D3 per day for 2-3 months, then running a follow up blood test to see where you are and adjusting your dosage accordingly.

I don’t have epilepsy, so I don’t have to take a psychoactive drug to manage this condition, but I do have to deal with my own version of a lifelong issue that compromises my ability to absorb and utilize vitamin D:  Osteoporosis runs in my family, and I know why. I have inherited a genetic SNP (single nucleotide polymorphism) that results in my vitamin D receptors not working very well, so I am less able to absorb vitamin D and need much more than the “average” person. (I need 10,000 IU of vitamin D3 daily, winter and summer, to get my vitamin D levels up into the optimal 60-80 ng/mL range.)

I’m sharing this with you because once I figured this out and supplied my bones with what they needed, my bones began to rebuild.  Almost 15 years ago now, my husband, Dr. Joe Pizzorno, ended up running one of the first genetic panels available that could evaluate SNPs involved in bone health. We decided to run this, at the time, very new test, because I was doing “everything right” and still losing lots of bone well before menopause.  The point here is that like my SNP, anticonvulsant drugs greatly lessen your ability to absorb and utilize vitamin D. But if you give your bones the amount of vitamin D that YOU need to maintain optimal (60-80 ng/mL) blood levels of this key bone-building nutrient, your bones can be on the road back to health as well.

Be sure you are getting sufficient vitamin K2 to benefit from your vitamin D-enhanced ability to absorb calcium

Vitamin D greatly increases your body’s ability to absorb calcium, but it does not tell your body what to do with the calcium you can now absorb. That is the job of Vitamin K, specifically, vitamin K in its K2 form. There are 3 forms of vitamin K available in supplements – vitamin K1, and two types of vitamin K2, MK-4 and MK-7. Vitamin K1 does help lower inflammation (which is good for your bones since too much inflammation activates osteoclasts, the specialized cells that break down bone), but K1 does nothing to activate the proteins that put calcium into bone (i.e., osteocalcin) and keep it out of your arteries (i.e., Matrix Gla-protein). Only vitamin K2 activates these proteins.

In the research, if vitamin K2 is taken in its MK-4 form, you need to take 45 milligrams a day for it to effectively help build bone, and you must take MK-4 in divided doses of 15 mg every 6-8 hours. This is because MK-4 is very rapidly metabolized and cleared from the body in, you guessed it, about 6-8 hours. The MK-7 form stays active in your body much longer –up to 3 days—so, taking only 120 micrograms once daily has been shown to not only activate osteocalcin and Matrix Gla protein (the calcium-regulating proteins), but to build up a reserve, so newly formed osteocalcin and MGP can be continuously activated.

YOU are going to need at least 120 micrograms each day of vitamin K2 in its MK-7 form. Since you are most likely going to be taking at least 5,000 IU of vitamin D3 daily, which will increase your absorption of calcium, you will also want to consider how much vitamin K2 you need to balance the calcium-absorbing effect of your vitamin D. Again, because of my genetic issues that cause me to need more vitamin D than the “average” person, I also need more vitamin K2. I take 240 micrograms (mcg) daily of the MK-7 form of K2. Since the psychoactive drugs needed to manage epilepsy (and also prescribed for depression, anxiety, insomnia, etc.) also increase your requirements for vitamin D, it may be better for you to take 240 mcg of MK-7 daily as well, and this should be quite safe.

Except for people on anticoagulant (blood thinning) medication, e.g., warfarin (Coumadin is the most popular brand name for this drug), vitamin K is extremely safe. No adverse events have been shown at doses of MK-7 even greater than 800 mcg/day. Those taking warfarin, however, need to work with their doctors to safely take vitamin K without disturbing their international normalized ratio [INR]. An INR that is too high indicates high risk of bleeding/inability to produce blood clots needed to prevent you from bleeding to death from even a tiny cut, while an INR that is too low suggests the warfarin dose needs to be increased to protect against excessive blood clot formation. The key factor here is maintaining a stable intake of vitamin K against which your doctor can calibrate the amount of warfarin YOU require.

Just presented research indicates that if you have been prescribed warfarin because you have heart failure, you may be able to discontinue it and use aspirin instead. This past Sunday, February 5, late-breaking research presented at the American Stroke Association’s International Stroke Conference 2012 in New Orleans showed that aspirin is just as effective as warfarin for heart failure patients. This study, which involved 2,305 heart failure patients, found no overall difference in risk of death or for either form of stroke (intracranial hemorrhage or ischemic stroke) between those who received aspirin and those who received warfarin. Researchers also noted warfarin had a higher risk of bleeding. The lead author of this study, Dr. Shunichi Homma, is quoted as stating, “Given that there is no overall difference between the two treatments and that possible benefit of warfarin does not start until after four years of treatment, there is no compelling reason to use warfarin, especially considering the bleeding risk.”[12]

Please share this information. An ounce of prevention – in the form of an intelligent, natural bone-building program – can help prevent much needless misery from these bone-busting drugs.

If, like Julie, you are having difficulty getting your doctor to monitor the effects on your bones of the medications you are being prescribed to manage your epilepsy, depression, anxiety or insomnia, please share this information with your doctor. The footnotes below cite the most recent papers in the peer-reviewed medical journals. (And they include the PubMed IDs [PMID #], making it extremely quick and simple to locate these papers on PubMed). Educate your doctor, so you can get the health care you deserve. If your doctor refuses to become educated, find another, more competent physician.


References:

  1. ^Pérez-López FR, Brincat M, Erel CT, et al. EMAS position statement: Vitamin D and postmenopausal health. Maturitas. 2012 Jan;71(1):83-8. PMID: 22100145
  2. ^http://en.wikipedia.org/wiki/List_of_benzodiazepines
  3. ^Luz Rentero M, Carbonell C, Casillas M, et al. Risk factors for osteoporosis and fractures in postmenopausal women between 50 and 65 years of age in a primary care setting in Spain: a questionnaire. Open Rheumatol J. 2008;2:58-63. PMID: 19088873
  4. ^A more complete listing can be found at http://en.wikipedia.org/wiki/SSRI#List_of_agents
  5. ^http://en.wikipedia.org/wiki/Atypical_antipsychotics#List_of_atypical_antipsychotics
  6. ^Bolton JM, Targownik LE, Leung S, et al. Risk of low bone mineral density associated with psychotropic medications and mental disorders in postmenopausal women. J Clin Psychopharmacol. 2011 Feb;31(1):56-60. PMID: 21192144
  7. ^Bolton JM, Metge C, Lix L, et al. Fracture risk from psychotropic medications: a population-based analysis. J Clin Psychopharmacol. 2008 Aug;28(4):384-91.
  8. ^Damsa C, Bumb A, Bianchi-Demicheli F, et al. “Dopamine-dependent” side effects of selective serotonin reuptake inhibitors: a clinical review. J Clin Psychiatry. 2004 Aug;65(8):1064-8. PMID: 15323590
  9. ^O’Keane V. Antipsychotic-induced hyperprolactinaemia, hypogonadism and osteoporosis in the treatment of schizophrenia. J Psychopharmacol. 2008 Mar;22(2 Suppl):70-5. PMID: 18477623
  10. ^O’Keane V, Meaney AM. Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia? J Clin Psychopharmacol. 2005 Feb;25(1):26-31. PMID: 15643097
  11. ^http://en.wikipedia.org/wiki/Tricyclic_antidepressants
  12. ^Aspirin similar to warfarin in stroke prevention, article available at http://news.nurse.com/article/20120205/NATIONAL02/102130013