A long list of diseases, drugs, and conditions cause osteoporosis. The osteoporosis specialist needs to be aware of these and how to diagnosis them in order confirm their presence and get the patient on the correct treatment for the problem causing her or his osteoporosis. Often this means referring the patient to another specialist. What makes osteoporosis a fascinating medical challenge is many people have more than one cause and some have no obvious cause other than being a white postmenopausal female. Studies show that in postmenopausal white women with osteoporosis, 1 in 5 will have a second cause other than being who they are, i.e. having the genetic osteoporotic complex.
Common Endocrine Diseases that Contribute to Osteoporosis
A benign tumor of usually one of the four small glands in the neck that regular serum calcium. It is simply treated with neck surgery to remove the overactive gland.
Due to calcium and/or vitamin D deficiency. This can be caused by chronic kidney disease.
Vitamin D deficiency
50% of white people and 75% of people of color have insufficient or deficient levels of vitamin D.
Common in women due to an autoimmune disease called Graves disease. It often goes undiagnosed for years until the doctor does a TSH and finds it suppressed below normal. The increased thyroid hormone levels accurate bone remodeling in an unhealthy manner causing bone loss.
Estrogen deficiency Androgen deficiency
Men who become testosterone deficient also become estrogen deficient because in men, the primary source of estrogen is from conversion of testosterone. In men, estrogen is needed to prevent loss of bone remodeling control just as it is in women, especially white men with Northern European ancestors because they often carry the polygenetic osteoporosis polymorphisms that becomes activated by estrogen deficiency. Women loose testosterone at menopause as well as estrogen. They still have DHEA produced in the adrenal gland that provides the average PM women with 35% of the androgens she had at age 30. Loss of estrogen triggers the polygenetic osteoporosis polymorphisms as discussed. Loss of androgens results in frailty because stem cells destined to become osteoblasts cannot differentiate into that cell type unless testosterone is present on its receptor within its nucleus. In the absence of testosterone, the stem cell changes into a fat cell and there are fewer osteoblasts to form new bone. Less bone formed with each bone remodeling cycle results in weaker bones that are frailer.
COPD and Osteoporosis
Emphysemic patients are simultaneously oxygen starved and intoxicated on carbon dioxide. The disease is the result of the progressive destruction of the gas exchange membrane where oxygen is absorbed from the air and carbon dioxide is released into the air. This results in chronic respiratory acidosis and anaerobic metabolic conditions prevailing through the patient. Bone is principal secondary acid buffer where carbonic acid is regenerated into bicarbonate. This process involves the passage of two H+ ions (acid ions) into the bone compartment with release of one Ca2+ into the serum. The 2H+ combine with a phosphorus ion, PO4-2 that was generated when it was abandoned by the calcium. To the extent that the calcium is not required for immediate metabolic purposes or new bone formation, it is in excess and the kidney will excrete it. Patients live with for many years with this chronic disease. The persistent loss of bone caused by its secondary buffer function adds up over time resulting in osteoporosis. Long acting inhaled glucocorticoids, poor nutrition, hypoxia, anaerobic conditions, reduced physical exertion and conditioning are important contributing factors for why these people develop severe osteoporosis.
Chronic bronchitis can be viewed as a chronic inflammatory disease that results in the release of significant toxic cytokines into the systemic circulation. These include, TNF alpha, IL6, Gamma INF and many others. These directly stimulate osteoclastic bone absorption causing bone loss and promoting osteoporosis. Some of the drugs essential for treatment of chronic bronchitis including inhaled, oral, and IV glucocorticoids are highly damaging to all bone cells.
Autoimmune Diseases Cause Osteoporosis
These diseases include Rheumatoid Arthritis, Psoriasis, Ulcerative Colitis, Crohn’s Disease and Systemic Lupus plus many more. They are discussed in detail in a separate section on this website. What ties all these conditions together and the factor that they share and the one that causes osteoporosis is that all are due to the action of cytokines released by immune system T-Cells. These cytokines cause the autoimmune primary disease the patient has but they also spill over into the blood and cause other diseases that respond to cytokines including osteoporosis. Flair of the primary disease, Rheumatoid Arthritis, also causes increased bone loss by some of the same cytokines that caused the joints to hurt in the patient with RA. They attack the joint, move into the blood circulate through the bone compartment, activate the osteoclasts directly through receptors on their cell surface and cause them to aggressively absorb bone. Control of the primary disease helps prevent the osteoporosis unless glucocorticoids are used to control it. Then the treatment of the primary disease becomes a new cause for you to become osteoporotic. Fortunately, your skillful doctor can manage these effects and treatment side effects. Several of the drugs listed in the Treatment section of this website are indicated for both osteoporosis and prevention of osteoporosis caused by glucocorticoids.
Chronic Liver and Kidney Disease
Cirrhosis of the liver
Cirrhosis causes chronic metabolic acidosis that relies on the bone system for secondary buffering resulting in bone loss by the same mechanism as in respiratory acidosis described above. The liver is the site of the metabolic transition of cholecalciferol to 25 OH dihydroxyvitamin D3, the partially active form of vitamin D and its storage form. If the livers productive capacity is impaired due to this illness, then they may not be able to synthesis this crucial step resulting in low vitamin D levels and poor calcium absorption. Nutrition is often poor in these patients and they feel tired and weak much of the time. It is common for them to be sedentary. These also contribute to their bone loss.
Chronic kidney disease
Today kidney function is measured for us on the commonly obtained lab test, the CMP or comprehensive metabolic profile. It is used for monitoring liver function, kidney function, and blood salts. The CMP reports the eGFR for estimated Glomerular Filtration Rate, one for African Americans, and one for Non-African Americans. The number provided is an accurate estimate of the quantity of blood passing through both kidneys every minute in ml. The kidney function is based on that value. When the eGFR is <60 ml/min the patient has Class III Chronic Kidney Disease. This is not kidney failure and almost no adults over 50 with CKD III ever go on to kidney failure, it is important for your doctor to know about this because in the background your body is compensating for this. The bones and the kidneys work together to control mineral metabolism. People with CKD III are at higher risk for some chronic diseases because of the compensations put in place by the bone and kidney to cope with the metabolic disturbance caused by CKD III. If the eGFR falls below 30 ml/min then CKD IV is said to be present. At that point, additional compensation occurs that involves other parts of the endocrine system including the parathyroid gland. Osteoporosis can develop in people with CKD if it is not recognized and the body is assisted in its efforts to compensate for the metabolic disturbances caused by reduced kidney function.
A genetic disorder that causes calcium to be leaked out of the kidney instead of be reabsorbed and is a cause kidney stones and osteoporosis. Seen often in families where multiple members have had kidney stones.
Psychiatric Disorders that Contribute to Osteoporosis
Excessive consumption of alcohol is associated with osteoporosis. The reason may have more to do with the other bad habits that typically accompany alcoholism. For instance, many alcoholics drink their calories rather than eat healthy meals, their calcium and vitamin D nutrition is poor and most importantly they do not give a GD either. Alcoholics are often found to be magnesium deficient, one of the rare groups to suffer this condition. Magnesium sufficiency is necessary for calcium to be absorbed from the gut. A magnesium deficient alcoholic is always calcium deficient. These people must become sober before they can be effectively treated, which they can be if they stop drinking.
This is the form of anorexia nervosa caused by excessive exercise seen in women primarily. It is covered in detail in a separate section on this website dedicated to AN.
The term dysthymia has now replaced our old friends depression and anxiety as diagnoses. Not many people realize dysthymia contributes to osteoporosis and one of the principal treatments for it SSRIs do too. Stress can trigger dysthymia it can cause stress too. Emotional stress results in release of cortisol, the body’s principal glucocorticoid from the adrenal gland. Cortisol in the short run is a powerful antidote to both physical and emotional stress and without it we could not survive. Chronic day in day out emotional stress experienced by those suffering with dysthymia however leads to sustained levels of cortisol above normal. This sets off a cascade of assaults on the patient’s health increasing their risk for everything from cardiovascular disease to cancer. It also doubles their baseline risk for osteoporosis.
Selective Serotonin Reuptake Inhibitors or SSRI include Prozac, Lexapro, and Paxil together with many others and similar drugs with similar side effects. Serotonin is a major neurotransmitter used in many places in the body for very different purposes. These drugs raise the level of serotonin in the brain, thereby effectively combating dysthymia. They also raise it in the bone compartment, inhibiting a protein-signaling pathway important for bone formation. The inhibition of this pathway reduces bone formation in people on SSRIs and this results in a higher rate of fractures. The relative risk is increased by 2x.
Bone clinicians and researchers suspect that there are one or more causes of primary osteoporosis. These would be a genetic disorder separate from the common polygenetic osteoporosis polymorphisms seen in white people. This or these conditions occur spontaneously rather than clustered in families. They have a predilection for men. A feature of their evaluation is very low bone mineral density on DXA with no other objective laboratory findings. These patients are quite often healthy, free of other significant disease and certainly free of diseases, conditions or medications known to cause osteoporosis. Treatment of these people is challenging. I have used ADFR activating them with a month of 1-34 teraparatide followed by a depressing dose of denosamab of 15 mg. After a resting period of two months, the 1-34 teraparatide activation is repeated. Harold Frost, MD, a brilliant orthopedist, and one of the early bone researchers and thinkers first proposed the ADFR approach. I used his recommended approach in the first research study I participated in 30 years ago and had a rare opportunity to meet him at the time. He conceived on many of the fundamental ideas on bone and mineral metabolism that we take for granted today.
My small group of patients with idiopathic osteoporosis had tried all other available therapies and failed to improve. The bone density did increase in some of these patients on ADFR and I then transitioned them all to Prolia. They have done well on Prolia, which is a surprising and unexpected finding.
Lifestyle Conditions that Contribute to Osteoporosis
The lack of physical stress placed on bone causes it to build down to a lower level. It “reads” your requirements based upon the physical forces you subject it to. Nature is frugal with its resources. Why should your skeleton conserve a bone strength and quantity required to support the lifestyle of an active adult when all you do is sitting around all day?
It is remarkable to see how much bone and muscle mass someone looses when placed at bed rest. They will literally wither away before your eyes. To prevent this requires that you get the person up regularly and have them bear weight if possible. This means sitting, standing, and walking. If they can do this during a serious illness that has put them in the bed at least a couple of times a day for a few minutes in will help prevent their loss of bone and muscle.
Immobilization due to Paralysis
Stroke, spinal cord injury, Parkinson, or MS are common causes of this. Bearing weight, any way you can manage it is the best approach. Sitting is better than lying. Standing is preferred to sitting and walking is the goal. Some find the parallel bars a good way to bear weight. This requires good upper body strength to prevent you from falling. Installing an overhead trapeze to help you move around the bed and get up into the sitting position as well as to help strengthen the upper body can be helpful. Use of 25 mg of pharmaceutical grade DHEA, as a hormone supplement will provide androgens needed by stem cells to become muscle and bone cell. I recommend MonoDEA 25 mg by Life Link sold on Amazon.com. It is a good quality product.
Tobacco causes chronic bronchitis and emphysema that result in chronic respiratory acidosis. This condition leads to osteoporosis.
Diet, Supplements, and Osteoporosis
Excess Calcium Supplementations
I have provided you with a detailed discussion on calcium supplements in another section on this website. The bottom line is do not take more than 300 mg of calcium as a supplement more than twice daily unless directed to by your doctor. Our diet is the best source of calcium and we should relay on it primarily. Taking too much calcium as a supplement, especially for those with Class III Chronic Kidney Disease causes cardiovascular disease. For others it can be a cause of kidney stones.
Excess Vitamin D
American’s are burdened by the notion that if one of something is good the two of that same thing must be twice as good. WRONG. If you want to get into trouble quickly, follow that ill-fated philosophy in medicine especially when dealing with an endocrine hormone like vitamin D. Yes, vitamin D is a hormone and one of the most potent and potentially dangerous hormones available to the public for purchase without direct physician supervision. Death from vitamin D happens because of too little or too much of this critical regulatory hormone. Too little and you become calcium deficient; develop Rickets or osteomalacia, and ultimately your heart stops beating. Too much and your calcium goes up too high, you become dehydrated, have kidney stones and go into cardiac arrest.
Vitamin D is a member of the steroid hormone family and is responsible for managing bone and mineral metabolism and the immune system at the DNA level. It controls over 1,000 human genes or 5% of the human genome.
The ideal blood level of 25 OH vitamin D3, which is the storage form of the vitamin and what is measured in the blood is between 40 ng/ml and 60 ng/ml. To obtain good bone health a level of 30 ng/ml is needed but for good immune health, you need a level of 40 ng/ml. I have found that pushing the 25 OH vitamin D3 level up much above 60 ng/ml suppresses parathyroid hormone levels. This is a direct effect of vitamin D on the gland and is something that is not supposes to happen according to the endocrinology literature I subscribe to. It does happen though and is something that I have seen repeatedly because it is my practice to measure both iPTH and 25 OH vitamin D on many of patients in osteoporosis clinic.
A good initial vitamin D3 dose for adults who are not fat or too thin is 2,000 IU per day in addition to the vitamin D you obtain from a multiple vitamin or calcium supplement. Overweight people need more vitamin D and thin people less. Checking blood levels after you have established a stable dose is the way to manage this. If you are above or below the treatment range, I recommend a rule of thumb given to me by Neil Binkley, MD who was one of the consultants for the Institute of Medicine Vitamin D panel that established the new guidelines. For every 100 IU of vitamin D3 taken, the serum 25 OH vitamin D3 will increase by about 1 ng/ml. This rule of thumb applies to normal weight people and would need to be adjusted for under or overweight persons.
I am a firm believer that you are what you eat. Those who eat poorly have poor health and is it any wonder why? Bone is a living tissue that is constantly at work removing the old and bringing in the new. It is a high-energy tissue. To function properly bone needs protein, carbohydrates, fats, vitamins, minerals, and everything else in the correct amounts or close enough. You know if you are not eating well. Get some help. One idea is to sign up for one of the meal services people who are trying to loose weight order.
Dietary calcium deficiency
The diet is the principal source of calcium to achieve and maintain bone health. I have provided guidance on diet for healthy bones throughout this website in various sections because it is so crucial. No medication is effective if your calcium intake is inadequate. If there is a medical problem causing calcium malabsorption, this can be corrected. If the problem is you do not want to use supplements and do not like calcium rich foods, then you are as is said up the creek without a paddle.
Drugs Treatment that Causes Osteoporosis
The potency of the inhaled steroids used for asthma and COPD is high enough to affect bone health. Your treating physician needs to bear this in mind and monitor your bone density while on these drugs. The drugs indicated by the US FDA for prevention of osteoporosis in people on glucocorticoids applies only to those on oral glucocorticoids at a dose of 7.5 mg per day or higher for 3 months or longer of continuous use. We do not have guidelines or an indication for prevention of osteoporosis in people on potent inhaled steroids.
I recommend everyone started on these drugs have a baseline DXA to see where you are now. Beginning calcium citrate 1 tablet twice daily and 2,000 IU of vitamin D3 is good idea. If you are already osteopenic, then discuss where or not to use of one of the agents approved for prevention of osteoporosis in people on glucocorticoids. Alendronate is a good option. If you are already osteoporotic, then treatment is definitely indicated now. Regular monitoring every year with DXA is a good way to determine if your treatment of prevention choice was effective.
Flonase, and Nasocort used for allergies are lower dose than those used for asthma and COPD but if abused will cause osteoporosis as well as atrophy of the nasal passage mucosa and increase your risk for a fungal sinus infection.
The US FDA has approved several drugs for prevention of osteoporosis in people taking oral steroids. These are Fosamax, Actonel, Reclast, and Forteo. The guidelines state that the oral dose of glucocorticoids to justify preventive therapy is 7.5 mg per day or higher for at least 3 months, or longer. They also state that using these drugs in people on lower doses has not been evaluated. My experience is that osteoporosis can be caused by smaller doses of glucocorticoids if given for prolonged periods, especially in the elderly. I would not hesitate to use the Fosamax in someone with osteopenia on 5 mg of prednisone daily for polymyalgia rheumatica for example. That autoimmune disease itself promotes osteoporosis. When long-term steroids are added to the equation, the outcomes can be poor.
Excess Thyroid Hormone
As muscle mass is lost due to the effect of loss of androgens, reduced physical activity, diet change, or aging a dose of levothyroxine that was perfectly adequate has now become excessive resulting in suppression of the TSH. Rarely does this iatrogentic form of hyperthyroidism become clinically apparent but it does have a metabolic influence on bone remodeling. Osteoclastic bone absorption is enhanced when thyroid hormone is in excess and more than the normal amount to bone is removed with each remodeling cycle. If prolonged this can result in skeletal weakening and fracture.
Elmiron indicated by the US FDA for the treatment of interstitial cystitis in women. There are no warnings on the drug label and no post marketing reports of osteoporosis or accelerated bone loss occurring in women using this product. There are no case reports of osteoporosis I have been able to find after doing a literature search. I have seen two patients who, in my opinion their osteoporosis was exacerbated by use of this drug.
It is biologically plausible that Elmiron could cause accelerated loss of bone because of its resemblance to heparin, a drug that has been a recognized cause of bone loss for years. My observations are not in any way proof. What is needed to find out is small 100 patient safety trial performed in postmenopausal women between the age of 50 and 60 with IC. The design should be double blind placebo controlled where DXA bone density before and after treatment with Elmiron for 1 year was the primary endpoint. If Elmiron use was found to be associated with bone loss, then an appropriate change would be made in its label and doctors advised to check their postmenopausal women’s bone density before therapy. If the patient was significantly osteopenic or osteoporotic, treatment would be indicated, similar to how this issue is address in women beginning aromatase inhibitor therapy.
If you are on Elmiron for IC and haven’t had a DXA, I recommend you do so.
Many anticonvulsants are metabolized in the liver by the same cytochrome p450 system that metabolizes regulatory steroid hormones resulting in there being insufficient or even deficient quantities available for proper metabolic control. It is common for anticonvulsants to be used chronically so the affect on people with seizure disorders that are often diagnosed in childhood or adolescence can be profound. Today most neurologists are aware that these drugs can cause osteomalacia by lowering the vitamin D level and compensate for this by prescribing vitamin D supplements. Few know how to supplement their patients properly, what serum levels are ideal, or how even monitor the patient’s vitamin D level if they recommended it. The entire family of essential regulatory steroid hormones is metabolized by the same liver enzyme and is reduced in the same way, as vitamin D has not been recognized by the neurologic profession.
The serotonin reuptake inhibitors have revolutionized therapy for dysthymia, what was referred to in the past as depression and anxiety. These two conditions have the same neurochemistry, which is a reduced level of the neurotransmitter serotonin. Drugs in the SSRI class, its related SNRI and the legacy antidepressants in the tricyclic class like Elavil all raise levels of serotonin not just in the brain where its beneficial effect on dysthymia is but also in the body as a whole. In the bone compartment, serotonin interferes signaling between bone cells required for bone formation. This results in a doubling of risk for osteoporosis. The standard therapies and estrogen/testosterone oppose these negative effects on bone health.
Proton Pump Inhibitors and H2 Blockers
The PPI class of drugs available OTC are wonderful therapy for gastroesphegeal reflux and gastritis. They include Prilosec, Nexium, Protonix and others. The H2 class are great too for the same indications but not as effective. They have fewer side effects though and are preferred over the PPIs if they work well for you. Some of these OTC brands include Zantac and Pepsid. Both classes contribute to osteoporosis by inhibiting stomach acid production. This prevents calcium from be released from the most commonly used supplement, calcium carbonate causing it to be malabsorbed. Stomach acid is required for the calcium found in food to be in the proper state of ionization. Calcium absorption occurs in first portion of the small intestine, known as the duodenum. If calcium is not in the free state and not properly ionized, the duodenal enterocyte calcium receptor is unable to firmly grasp calcium and pull it into the cell as it passes by. This results in its malabsorption. For people who need to use these stomach medications, there is a simple remedy. Use one calcium citrate table twice daily. Calcium citrate dissolves in the stomach without need of acid and when it does it is already in the proper ionization state for optimal absorption by the small intestine