Osteomalacia, Osteoporosis

Osteomalacia refers to the reduction of the mineralization of bone. The problem of demineralization of bone is often confused with loss of whole bone tissue (osteoporosis). Bone stores 99% of body calcium and calcium salts, laid down in a soft protein matrix, are responsible for the hardness of bones. Long-term calcium deficiency and/or vitamin D deficiency leads to bone thinning or osteomalacia.

 

The term osteoporosis now refers generally to loss of bone density and increased risk of fractures, especially of the spine and hips. Originally, the term referred only to the loss of the bone matrix - a soft tissue and did not refer to the state of mineralization of the bone. With loss of bone matrix, there is less to mineralize and bone density decreases regardless of mineral status. 

Stephen J. Gislason MD

A high calcium intake and adequate Vitamin D will promote optimal bone mineralization in youth and decrease the rate of bone-mineral loss in the later postmenopausal period. Lack of Vitamin D in children leads to Rickets -soft, poorly mineralized bone that bends easily. In older women, a high plasma level of vitamin D enhances calcium absorption, whereas high sodium, protein, alcohol and caffeine intakes will cause increased urinary losses and negative calcium balance. Other regulatory changes and/or vitamin D deficiency may alter the balance between calcium absorption from the bowel and excretion from the kidney. 

 

The term "Osteoporosis" refers to a loss of total bone mass and not just bone thinning due to calcium deficiency. Bone loss in adults increases the risk of bone fractures and may contribute to the loss of teeth in healthy postmenopausal women. Low bone mass in women is attributed to a genetic tendency, estrogen deficiency and lack of regular physical activity.

Women, fearing the stooped posture of old age, are eager to take milk or calcium supplements. TV ads, promoting calcium ingestion, show the degenerating profiles of an aging woman and are deceptive. Osteoporosis is more a problem of disuse atrophy, with age-related reduction of bone growth-factors than of calcium deficiency. Daily, weight-bearing exercise is the best method of maintaining bone-growth at any age. Women over 50 years of age show the most bone thinning because of deficiency of anabolic sex hormone production, especially estrogen and declining physical activity. In early menopause, estrogen replacement is effective therapy for conserving bone mass in women.  

Bone atrophy can be reduced in post menopausal women with hormone replacement, taken from age 50 onward. Cyclic estrogen and progesterone supplementation in post-menopausal women is the currently recommended strategy. Progesterone acts in concert with estrogen to increase bone formation, and decrease bone resorption, with a net increase in bone mass and strength. Low dosage estrogen (0.3 mg/d - day 1 to 25 of arbitrary cycle month), a progestogen (day 16-25), with 1000 mg of Calcium  plus other minerals - manganese, copper, zinc - are recommended as part of a treatment program for post-menopausal osteoporosis. Postmenopausal women given calcium alone show progressive bone de-mineralization. Vitamin D is added  at 800 to 1000 iu per day and doses up to 4000 iu per day have been useful in postmenopausal women with established osteopororosis. MDF Latex-Free Blood Pressure Cuff Newborn Single Tube

Measuring Bone Mineral Density.

The measurement of bone mineral density is is "a poor way of predicating which woman will suffer from a hip or spinal fracture..." according to Dr. Ken Basset of the B.C. Office of Health technology assessment. An English study ( Law et al Br. Med J,1991:303:453-9) showed that low bone density measurements only identified 6% of women who later suffered fractures. The lifetime risk of hip fracture in women is about 18% and the incidence increases with age.  One of the reasons for doing a bone density measurement is to focus attention  the need for preventive strategies in postmenopausal women. The test can be replaced by a policy that states that all postmenopausal women need preventive strategies, starting with daily exercise, proper nutrition and optionally, hormone replacement therapy if there are no contraindications. tops online store

Biophosphonates

Alendronate (Fosamax) 5.0 to 10.0 mg per day prevents osteoporosis in younger postmenopausal women, an alternative therapy for women who cannot take hormone replacement therapy (HRT) and an adjunctive therapy for women on HRT. The drug also prevents steroid induced osteoporosis should be considered for use in all patients who require long-term steroid therapy.  In multicenter randomized study  (Fracture Intervention trial, reported 1998 at the European Congress of Osteoporosis ), Alendronate decreased the rate of hip fractures by 58%( at mean follow-up period of 3.8 years) in postmenopausal women who took 5 mg/day for 24 months then 10 mg per day. In another study, combined therapy with Alendronate 10 mg/day, Vitamin D 4000 iu/day, and 1000 mg Calcium/day had increases in bone density 2-5 times greater at 12 months than women on HRT alone.

Calcitonin (salmon hormone nasal spray) has also been effective in reducing spinal fracture rate in women over a 4 year period; the women already had one spinal fracture- 200 IU per day over 4 years reduced the risk of fracture by 36%. Bone density increases of .7 to 1.6% were observed.

Raloxifene (Evista 60-120 mg/day), an estrogen hormone receptor modulator reduced spinal fracture rates by 38% in a group of postmenopausal women who already had one fracture.

Other Minerals

Silicon is another mineral with a potential influence on bone growth. It is essential in many animals for normal bone growth, but is not usually considered in human physiology. Copper and manganese are also essential for normal bone matrix formation, and must be considered in the overall nutrient equation.

Calcium Supplements

Types of calcium supplement vary a great deal. The cheapest, common supplement is Calcium Carbonate ("Tums"), made from limestone, or oyster shells. The range of absorption efficiency is great, 7% to 68% in one study. There are problems with this calcium supplement in large amounts over a long period of time. Calcium carbonate is an antacid which reduces stomach acidity and may interfere with the digestion of food. It causes "rebound" hyperacidity after it leaves the stomach. It blocks its own absorption. It may be poorly absorbed, and bind other minerals and vitamins. Excess calcium is likely to appear as kidney or gall-bladder stones. More soluble calcium compounds are better, but are usually more expensive. Calcium citrate is not  soluble. Calcium glycerophosphate is the most soluble compound and is used in Alpha OMX and Alpha VMX. Another reason that calcium Glycerophosphate is ideal is that phosphate is required for bone formation. Calcium supplements alone will inhibit phosphate absorption from food.

Calcium intake recommendations, to be realistic and effective will have to take into account the type of calcium chosen and the variables of absorption in each individual.

Calcium absorption from GI tract is regulated by vitamin D and parathyroid hormones. Without parathormone you cannot actively transport calcium through GI tract. In normal circumstances less than 1.0 grams of calcium per day is adequate, but without parathormone, 4-6 grams per day may be required along with excessively high doses of vitamin D, up to 50,000 IU per day - 250 times the RDA!

Each mineral works best in proportion to other minerals. Calcium is usually referred to magnesium; and the ratio range should be 2-4; Ca/Mg. Vitamin D  and calcium intake recommendations must therefore take into account the kind of calcium, the amount of vitamin D in the diet, the amount of sun exposure, the activity of parathormone, the dietary intake of binding substances like Phytic acid, and competition of calcium with phosphorus, magnesium and other minerals. Deciding calcium intake recommendations, is not simple. There is likely to be a wide margin of error in any general "recommended daily allowance".

No Bones About It: Nerve cell protein controls bone formation

The top dogs in a big corporation might fire the entry-level interns, but they send the pink slips through middle managers. Similarly, when the body's head honcho--the central nervous system--authorizes bone construction, an intermediary neuronal protein delivers the work order, researchers have now found. The results clarify how the obesity-preventing hormone leptin thins bones and also suggest novel approaches for strengthening them. Furthermore, the findings bolster the validity of a new idea--that the brain controls bone metabolism through nerves in addition to the bloodstream.

Animals constantly break down and rebuild their bones to keep their skeletons healthy. The process requires a balance between the actions of cells that destroy and create bone, called osteoclasts and osteoblasts, respectively. When the equilibrium goes awry, diseases such as osteoporosis--in which the skeleton thins, weakens, and cracks--set in. A few years ago, researchers discovered that leptin, which diminishes appetite by spurring other blood-borne molecules into action, also reins in osteoblasts. As a result, rodents that lack leptin develop dense bones. Scientists already knew that the brain emits hormones that ramp osteoclasts up or down. But leptin seemed to control bone growth through the central nervous system (CNS) rather than by dispatching molecules to the tissue through the bloodstream. In the brain, leptin quenches production of a second hormone called neuropeptide Y (NPY). A receptor protein called Y2 binds NPY and coordinates communication between neurons in the CNS, suggesting that it could relay nerve signals between brain and bone.

To examine Y2's role in bone maintenance, Badlock and colleagues engineered a rodent strain that lacked the gene for the receptor. Animals devoid of Y2 had twice the bone mass of normal mice. Without Y2, osteoblasts laid down bone twice as fast as usual, whereas osteoclasts behaved normally. The results suggest that NPY sends a signal through Y2 to slow down bone fabrication.

Next, the researchers probed whether Y2 controls bone growth via the CNS. They selectively removed the Y2 gene from the hypothalamus, a brain region that regulates the body's hormonal systems. Adult animals that lacked Y2 only in the hypothalamus grew thick bones. In addition, the team measured concentrations of hormones known to be affected by leptin. The neuroscientists found no changes in major hormone networks in mice that lack Y2. Together, these results suggest that Y2's influence on bone acts directly through the CNS and does not involve changes in the circulating hormones that leptin alters.

Endocrinologist Gerard Karsenty at Baylor College of Medicine in Houston, Texas, says that this work is an "important verification" for the young theory that the CNS controls bone metabolism. In addition, study leader and neurologist Herbert Herzog of the Garvan Institute of Medical Research in Sydney, Australia, says that Y2 might be an attractive target for new bone disease therapies. Compounds that block Y2 might spur bone growth without also releasing leptin's hold on body weight. That result would be good news for osteoporosis sufferers, who could use a taste of strong bones but without all the fat.

--Mary Beckman

P. A. Badlock, A. Sainsbury, M. Couzens, R. F. Enriquez, G. P. Thomas, E. M. Gardiner, H. Herzog, Hypothalamic Y2 receptors regulate bone formation. J. Clin. Invest 109, 915-921 (2002).

Alpha OMX  To Prevent and Treat Osteoporosis