Skeleton Pirate

Skeleton Pirate
Artist: LindaB


Have you experienced, or read about, negative, and even dangerous, side effects from Fosamax (alendronate), Boniva (ibandronate), Actonel (risedronate), and other bisphosphonates prescribed for osteoporosis? If you have, then rest assured there is a safe, effective treatment for this condition. Strontium, primarily in the form of strontium citrate, is taken orally once a day.

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Tuesday, September 13, 2011

Antiresorptive, Anabolic, And Dual-Action Osteoporosis Drugs

Osteoporosis drugs can be divided into three categories: antiresorptive drugs that slow bone breakdown (resorption), anabolic drugs that build new bone, and dual-action drugs that both slow bone resorption and build new bone. Most approved osteoporosis drugs are antiresorptive. These slow bone loss and help fill in the remodeling spaces. All antiresorptive agents reduce the risk of vertebral (spinal) fractures and reduce markers of bone turnover. These markers are substances in the blood and urine that reflect the activity of the bone cells involved in breakdown and formation.

Antiresorptive medications include bisphosphonates, selective estrogen receptor modulators (SERMs), hormone replacement therapy (HRT), and calcitonin. Bisphosphonates include alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast). The only approved SERM is raloxifene (Evista). HRT includes several agents: Premarin, Prempro, Estrace, Estraderm, and Climara. Calcitonin is a polypeptide hormone secreted by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish. Miacalcin® (calcitonin-salmon) Nasal Spray is a synthetic polypeptide of 32 amino acids in the same linear sequence that is found in calcitonin of salmon origin. Miacalcin is also available as an injection.

The newest drug in the antiresorptive category is denosumab (Prolia), an injection administered subcutaneously once every six months. Prolia binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Prolia prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.

In clinical trials in women with postmenopausal osteoporosis, treatment with Prolia resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry. The significance of these findings and the effect of long-term treatment with Prolia are unknown. The long-term consequences of the degree of suppression of bone remodeling observed with Prolia may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing.

Antiresorptives do not build bone beyond what is produced to help fill the remodeling spaces. Bone-building (anabolic) drugs, on the other hand, stimulate bone formation by increasing the activity of the cells known as osteoblasts. The only such medication approved in the U.S.A. for treating osteoporosis is teriparatide (Forteo), a form of human parathyroid hormone (PTH). The drug comes as a daily injection, which can be self-administered. PTH produces larger increases in BMD than antiresorptives do. It also improves bone microarchitecture. However, it is prescribed for no more than about two years because its long-term safety and efficacy are unknown. Most experts recommend that antiresorptive drugs be stopped during PTH therapy and restarted after the course of PTH is complete.

Strontium ranelate is a compound that incorporates the element strontium, which is found in trace amounts throughout the skeleton. Results from Phase III trials conducted by French researchers suggest that strontium ranelate may reduce vertebral fractures about as well as bisphosphonates. The drug is believed to work by decreasing bone breakdown and increasing bone buildup. This prescription drug is not available in the U.S.A., but strontium citrate can be purchased as a supplement.

My opinion is that the antiresorptive drugs are flawed models as osteoporosis drugs. If we keep slowing bone breakdown without building new bone, we eventually end up with very old, weak bones. Long-term suppression of bone remodeling by Fosamax and other bisphosphonates has led to osteonecrosis of the jaw and atypical femur fractures in some patients. Better models are bone-building (anabolic) drugs (i.e. Forteo) and dual-action agents (i.e. strontium ranelate, strontium citrate) that decrease bone breakdown and increase bone buildup.


Wolfy said...

Very interesting post. Still so much we don't know about osteoporosis drugs. I would like more studies done on the effects of stronium citrate on kidney function, the toxicology of strontium citrate, and the role of strontium in kidney stone formation.

I would also like to see data from the new hi-res, computer-enhanced digital MRI to determine the ratio of living bone to dead bone. It might someday replace the DexaScan which is not very accurate.

BoneLady said...


Recent advances in micro-imaging technology, notably microcomputed tomography (microCT) and magnetic resonance imaging (MRI) make it possible to image trabecular bone in vitro in cadaveric specimens or bone biopsies, and more recently in vivo, and to analyze the resulting images using digital image processing. Trabecular bone strength is related to thickness, number density,and orientation of the trabeculae.

In “Three-Dimensional Digital Topological Characterization of Cancellous Bone Architecture,” a study by Punam K. Saha, Bryon R. Gomberg and Felix W. Wehrli, "the potential of digital topology as a means to quantitatively characterize the 3D architecture of cancellous bone networks is demonstrated. An important property of the proposed method is its ability to uniquely classify each bone voxel after binarization and skeletonization, therefore providing local connectivity information. The known conversion of plates to rods during normal aging, especially in osteoporosis, may be followed quantitatively by measuring the surface-curve ratio, or an erosion index, as composite parameters directly amenable from the analysis. The dramatic variations in cancellous bone morphology occurring among subjects of different age and disease state are illustrated with virtual bone biopsies derived from in vivo MR micro images. Finally, because the mechanical properties of cancellous bone networks are highly dependent on their structural organization, the method may be suited for strength assessment in vitro and prediction of fracture risk in vivo."

Wandering Skeleton

Wandering Skeleton
Artist: Joel Hoekstra

Osteoporotic Bone

Osteoporotic Bone

How Strontium Builds Bones

Strontium is a mineral that tends to accumulate in bone. Studies have shown that oral doses of strontium are a safe and effective way to prevent and reverse osteoporosis. Doses of 680 mg per day appear to be optimal. See my "For More Information About Strontium" links section.

Osteoporosis is caused by changes in bone production. In healthy young bones there is a constant cycle of new bone growth and bone removal. With age, more bone is removed and less new bone is produced. The bones become less dense and thus more fragile.

Scientists believe that strontium works in two ways. It may stimulate the replication of pre-osteoblasts, leading to an increase in osteoblasts (cells that build bone). Strontium also directly inhibits the activity of osteoclasts (cells that break down bone). The result is stronger bones.

When taking strontium, be sure to take 1200 mg calcium, 1000 IU vitamin D3, and 500 mg magnesium daily. It is best to take strontium late at night on an empty stomach. Calcium and strontium may compete with each other for absorption if taken together.