Bone Remodeling and Bone Drugs

Bone remodeling is the process by which your body makes and recycles bone. If you understand bone remodeling, you can more fully understand how bone drugs work and what they do in your body.

In this document
Bone Cells and Bone Remodeling
Osteoporosis Drugs
Antiresorptive Agents
(Fosamax, Binosto, Boniva, Actonel, Atelvia, Reclast,
Calcitonin, and estrogen)
Anabolic Agents
(Evenity, Forteo, Tymlos)

Related Articles (WEB)
Study Finds Popular Bone Drugs Actually Cause Fractures
Most Osteoporosis Drugs Don’t Build Bone. This One Does. (Evenity carries a risk of heart attack.)
Medicines Like Fosamax: How Well Do They Treat Osteoporosis?

Bone Cells and Bone Remodeling

Bone remodeling is the continuous cycle of bone building and bone resorption. Bone building is the process by which your body adds new bone tissue to your skeleton, and bone resorption is the process by which your body removes (dissolves and assimilates) old bone tissue. Bone remodeling is a continuous process in your body that is regulated by calcium levels, the thyroid gland, and the parathyroid glands. It also requires proper nutrition.

The three types of cells in bone marrow that enable bone remodeling are osteoblasts, osteoclasts, and osteocytes. Each of these cells has a similar, but distinct, role in the health of the human skeleton. The main initiators of bone remodeling are 1) mechanical stress on the bones, and 2) hormonal controls that maintain calcium levels.

Mechanical stressors are running, walking, weight lifting, yoga, Qi Gong and other weight bearing activities that result in microscopic changes to the bone. If the microscopic changes are not repaired through bone remodeling, they get larger, and can over time cause a broken bone when under minimal stress.

Research shows that bone-building markers increase in your blood or urine in as little as 12 seconds of subjecting a bone to mechanical stress, and stop after 72 seconds. Bone markers are chemicals that show up in the blood and urine and can be identified through blood and urine testing.

Hormonal controls are managed by the thyroid and parathyroid glands.

• Thyroid gland: The calcitonin cells (c-cells) in the thyroid gland produce calcitonin. Calcitonin reduces the calcium level in the blood and acts on the calcitonin receptors in bones to prevent the breakdown of bone. Both of these actions build bone (increase bone density).
• Parathyroid glands: The parathyroid glands produce parathyroid hormones that stimulate osteoclasts to resorb (dissolve and assimilate) old bone cells and send the calcium stored in the resorbed bone cells into the bloodstream. When the blood-calcium level gets too high, the parathyroid gland stops producing parathyroid hormones. The drop in parathyroid hormones causes the blood calcium level to fall, which triggers bone building.

Hormones: Your body produces parathyroid hormone and vitamin D (vitamin D is a hormone) to help your body maintain calcium levels. Estrogen reduces the number of osteoclasts, which helps regulate the balance between osteoblasts and osteoclasts in favor of bone building.

• Parathyroid hormone maintains calcium levels and stimulates bone formation and resorption.
• Calcitrol (from vitamin D) stimulates the intestines to absorb enough calcium and phosphorus.
• Calcium and phosphorus enable your body to build strong, healthy bones.

See Natural Ways to Improve Bone Health for information about nutrients, estrogen, and estrogen levels.

Osteoblasts (Bone Building)

Mechanical stressors stimulate osteoblasts to create collagen. Collagen is the organic component in bone and its role is to stimulate new bone growth and repair. Bone growth and repair strengthen the bones so they can handle the mechanical stresses put on them. Bones grow and remodel themselves based on the demand put upon them.

Osteoblasts move inside the bone, stick in the tissue, and turn into osteocytes (mature bone cells).

Osteocytes (Bone Building and Bone Resorption)

Mature osteocytes embedded in mineralized bone produce sclerostin. Sclerostin is a protein that inhibits bone formation and enhances the death of osteoblasts. Sclerostin is kept in balance as follows:

• Bone Building: Parathyroid hormone and weight-bearing exercise both decrease sclerostin and increase IGF-1, a hormone associated with bone building.
• Bone Resorption: Glucocorticoids (a class of steroid hormones made by the adrenal glands) enhance sclerostin, which enhances bone resorption.

Osteoclasts (Bone Resorption)

Osteoclasts manage the continuous break down and dissolution of mature (dead) bone cells. They dissolve the organic collagen and the inorganic calcium and phosphorus of old bone. Calcium and phosphorus, liberated by the breakdown of the mineralized bone, are released into the bloodstream. See Bone Resorption in Wikipedia.

Low amounts of any of the following tip the bone building and bone resorption ratio in favor of resorption: calcium, vitamin D, magnesium, phosphorus, vitamin K, probiotics, or estrogen levels.

• Vitamin D promotes the absorption of calcium
• Magnesium is needed for your body to make calcitonin
• Calcium needs Phosphorus to maximize its ability to make strong bones
• Vitamin K plays a critical role in how your body deposits calcium into new bone
• Probiotics make your digestive system strong so your body can synthesize gut vitamins
• Estrogen reduces the number of osteoclasts, which helps regulate the balance between osteoblasts and osteoclasts.

See Natural Ways to Improve Bone Health for information about the above nutrients and estrogen.

Osteoporosis Drugs

The next sections list common osteoporosis drugs by their classifications. It also explains what each classification of drugs does in your body, and for each drug, lists a few of the side effects for each drug. To get complete information on the side effects, you can look the drugs up on the web or talk to your doctor.

Antiresorptive Agents

Antiresorptive agents slow or block the resorption of bone by osteoclasts. Bone resorption is the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. 

Antiresorptive agents increase bone density using various strategies to slow bone resorption. This means old bone is kept and can result in brittle bones over time, which is why these drugs have a time limit on how long to take them. People with brittle bones are more likely to break their bones when they fall.

Dr. Fishman at Manhattan Physical Medicine says that yoga makes bones more pliable, which makes them more likely to withstand a fall. He also points out that smaller people don’t fall as far or take as much weight with them, which makes their bones less likely to break in a fall, especially if the bones are not brittle, but pliable.

In contrast, large people stimulate bone remodeling more easily because their size and weight put more demand on the bones.

See this eye-opening article on the FDA website, Possible Fracture Risk with Osteoporosis Drugs, and this one from Health Sciences Institute, Study Finds Popular Bone Drugs Actually Cause Fractures.

Bisphosphonates

Bisphosphonates inhibit bone resorption. They are combined with technetium 99m to enhance bone imaging for detecting bone problems such as osteoporosis and/or fractures. The main side effects for this class of drugs are gastrointestinal irritation such as stomach pain, heartburn, and acid reflux. Some of these drugs also have urinary tract side effects.

• Alendronate (Fosamax) oral tablet or solution daily or weekly
• Alendronte (Binosto) effervescent weekly tablet
• Ibandronate (Boniva) monthly oral tablet
• Ibandronate (Boniva) IV injection every 3 months
• Risendronate (Actonel & Atelvia) daily, weekly, once a month, twice a month, oral tablet
• Risendronate (Atelvia) weekly oral tablet
• Zelodronic Acid (Reclast) yearly IV infusion

RANK Lignand (RANKL) Inhibitors

RANKL inhibitors prevent the development of osteoclasts, which are cells that break down old bone.

• Denosumab (Prolia) 6 monthly injection. Example side effects: back pain, arm pain, muscle pain, bladder infection, and high cholesterol. See this article Bone Drug Prolia can Lead to Fractures and Bone Death.

Calcitonin

Calcitonin is a hormone secreted by the Calcitonin cells (C cells) in the thyroid gland. It reduces calcium in the blood and acts on the calcitonin receptors in bones to prevent the breakdown of bone (keeps old bone around), which increases bone density.

Calcitonin is reserved for the treatment of postmenopausal osteoporosis in women when other treatments for osteoporosis are ineffective, not tolerated, or not desired. The FDA discourages its use, saying the risks of malignancy outweigh its benefits. Nasal side effects are common and blood calcium levels must be within the normal range before treatment begins.

• Calcitonin (Fortical) daily nasal spray. Example side effects: nasal irritation, nose bleeds, runny nose, and sneezing.
• Calcitonin (Miacalcin) injection. Example side effects: blurred vision chills or fever cough difficulty breathing difficulty swallowing.

Estrogens (Hormone Replacement Therapy)

Studies have found that in men and women, estrogens play an important role in the regulation of bone mass and bone strength by managing the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. Not enough estrogen can cause the balance between bone formation and bone resorption to tip in favor of resorption, which over time results in bone loss. Estrogen reduces the number of osteoclasts, which helps regulate the balance between osteoblasts and osteoclasts. See Natural Ways to Improve Bone Health for more information about hormone replacement therapy (HRT).

• Oral tablet once a day (multiple brands)
• Transdermal patch once or twice a week (multiple brands)

Estrogen Agonists/Antagonists, aka SERMS

Selective Estrogen Receptor Modulators (SERMs) are agents that activate some estrogen receptors, but not others. This means they have an estrogen-like effect on target tissues such as bone, without affecting other tissues that have estrogen receptors. See Natural Ways to Improve Bone Health for more information about hormone replacement therapy (HRT) and estrogen receptors.

• Raloxifene (Evista) daily oral tablet. Example side effects: bloody or cloudy urine, throat congestion, and chest pain.

Tissue-Specific Estrogen Complex (TSEC)

This type of bone drug pairs an estrogen or estrogens with a SERM (described above). The goal is to provide the clinical benefits of each component (estrogen and SERM) for improved tolerability. A TSEC that contains the SERM bazedoxifene and conjugated equine estrogens, such as Premarin, relieves hot flashes, improves vulvovaginal atrophy and its symptoms, and prevents loss of bone mass without stimulating the lining of the uterus (endometrium). Stimulating the endometrium might lead to endometrial cancer.

• Estrogen/Bazodoxifene (Duavee) daily oral tablet. Example side effects: muscle spasms, nausea, vomiting, diarrhea, and indigestion.

Anabolic Agents

This is a group of synthetic testosterone derivatives with pronounced anabolic (building) properties, and relatively weak androgenic (male characteristic promoting) properties. Anabolic agents stimulate the growth and repair of body tissues in diseases or states that promote the wasting of tissue (such as osteoporotic bone loss).

Sclerostin Inhibitor

Sclerostin is made by bone tissue. Its role is to inhibit bone formation and enhance the death of osteoblasts (bone-forming cells). This type of drug inhibits sclerostin to encourage bone formation and prolong the life of osteoblasts.

• Romosozumab-aqqg (Evenity) monthly or yearly injection. Example side effects: Fast heartbeat, skin rash, and chest tightness. See the NY Times article: Most Osteoporosis Drugs Don’t Build Bone. This One Does that explains the drug and carries the following notice at the bottom:
  
  This drug was approved only for postmenopausal women with a high risk of fracture, and will carry a warning on its label that it may increase the risk of heart attack or stroke, the F.D.A. said.

Parathyroid Hormone Analogs

Forteo and Tymlos are lab-made versions (analogs) of human parathyroid hormone (PTH). Both drugs are similar to the PTH that your body produces naturally. Forteo is also available as a generic drug called Teriparatide. Both medications are self-administered daily with an injection pen.

The drugs in this category both replicate the bone-producing effects of parathyroid hormone. These medications only work to build bone, so physicians will also recommend a bisphosphonate medication to decrease the rate that bone is destroyed to slow down your body’s natural rate of bone loss. This is so you don’t lose more bone than these drugs help you to build.

• Teriaparatide (Forteo) daily injection. Example side effects: dizziness, nausea, headache, rapid heartbeat, fatigue, stomach pain, and vertigo. More serious but less common side effects include bone cancer, decrease in blood pressure, increase in blood calcium, and an increase in urine calcium.
• Abaloparatide (Tymlos) daily injection. Example side effects: pain, nausea, and joint aches. More serious but less common side effects include bone cancer, increased calcium in the blood, worsening kidney stones, and a decrease in blood pressure.

For more information, see What is the Difference Between Tymlos and Forteo?