Bone Loss

Overview

Bone loss is a weakening of the bones and may be caused by aging, cancer, or cancer treatment. Bone loss may be diagnosed if the results of a test (called a bone scan) indicate weak bones. However, many individuals do not realize they have bone loss until they experience a fracture. Treatment for bone loss may consist of surgery to repair a fracture, radiation to treat cancer in the bones, or drug therapy, including the newer bisphosphonate drugs, which can also prevent bone loss.

What is Bone Loss?

Bone loss occurs when there is decreased calcification or reduced density of the bones. The result is weak bones that are at increased risk of fracture. Bone loss can occur as part of the normal aging process or as a complication of cancer or cancer treatment.

What  Causes Bone Loss?

Normal bone is constantly being broken down and rebuilt, a process called remodeling. Every week, humans recycle 5% to 7% of their bone mass. Bone loss occurs when there is a disruption to this normal remodeling activity in the form of an increase in the breakdown of bone without a comparable increase in bone building.

Bone loss may occur as a result of:

  • Osteoporosis (a weakening of the bones related to aging and other factors)
  • Hormonal therapy for the treatment of breast and prostate cancer
  • Chemotherapy for the treatment of cancer in women
  • Bone Cancer or Bone Metastases (cancer that has spread to the bones)

Does Cancer Treatment Contribute to Bone Loss?

Some cancer treatments can increase bone loss. Hormonal therapies administered in the treatment of breast and prostate cancer can leave patients more susceptible to bone loss. Treatment with chemotherapy may also lead to bone loss in some patients.

Patients that are diagnosed with early stage breast or prostate cancer often receive long-term treatment with hormonal therapy. The goal of hormonal therapy is to reduce the levels of the hormone estrogen in women and androgens (male sex hormones) in men, since these can stimulate the growth of breast and prostate cancers. However, the sex hormones also play an important role in maintaining healthy bones, and reducing their levels may cause bone loss. Women undergoing hormonal therapy for breast cancer have significant rates of bone loss1 that are at least double those reported during early menopause, a time that women typically experience profound bone loss. For men receiving hormone therapy and orchiectomy (removal of one or both testes) in the treatment of prostate cancer, a loss of hip bone mineral density of up to 9.6% has been reported in the first year after treatment.2 Furthermore, many women who undergo chemotherapy experience ovarian failure after treatment and have increased bone loss as a result.3, 4

What are the Signs and Symptoms of Bone Loss?

Bone loss is sometimes called a “silent disease” because it occurs without symptoms. People may not know they have bone loss or low-density bones until they become so weak that a sudden strain, bump, or fall causes a fracture.

Fractures can occur in any bone. However, fractures to the hip or spine are particularly troublesome and are often a sign of bone loss. When these bones are healthy, they can withstand significant impact; however, when an individual has low bone-density, even a minor fall may result in a fracture.

How is Bone Loss Diagnosed?

Bone loss is diagnosed with a bone density scan. DEXA ( Dual Energy X-ray Absortiometry) scanning is the most widely used method for measuring bone mineral density. DEXA scanning rapidly directs x-ray energy, alternating from two different sources, through the bone being examined. Once the x-rays have passed through the bone, their strength is recorded. Bone density or bone loss is calculated from the amount of energy that travels through the bone and is picked up by the detector. The minerals in bone, predominantly calcium, weaken the transmission of the x-rays through the bone. The more dense the bone is, the fewer x-rays get through to the detector. The use of two different x-ray energy sources greatly improves the precision and accuracy of the measurement.

How Can Bone Loss be Prevented?

Bisphosphonate drugs can effectively prevent loss of bone that occurs from metastatic lesions, reduce the risk of fractures, and decrease pain. Bisphosphonate drugs work by inhibiting bone resorption, or breakdown. Bone is constantly being “remodeled” by two types of cells: osteoclasts, which break down bone; and osteoblasts, which rebuild bone. Although the exact process by which bisphosphonates work is not completely understood, it is thought that bisphosphonates inhibit osteoclasts and induce apoptosis (cell death) in these cells, thereby reducing bone loss. There is also evidence that these drugs bind to bone, thereby blocking osteoclasts from breaking down bone.

Cancer cells release various factors that stimulate osteoclastic activity, causing increased breakdown of bone. By inhibiting osteoclasts, bisphosphonate drugs effectively reduce the detrimental impact that cancer cells have on bone density. An analysis of the results from 30 clinical trials demonstrates that patients with bone metastases treated with a bisphosphonate had a delayed time to skeletal fractures, a reduced need for radiation therapy to treat bone metastasis, a reduction in hypercalcemia (high blood levels of calcium), and a reduction in the need for orthopedic surgery.5

Bisphosphonate drugs that are FDA-approved for the treatment of cancer-related skeletal complications include Zometa® (zoledronic acid) and Aredia® (pamidronate). Of these two drugs, Zometa® appears to demonstrate the strongest activity. An added benefit of Zometa® is that it is administered in a dose ten times lower than Aredia®, which considerably reduces the administration time from several hours to 15 minutes, resulting in a more convenient regimen for patients.

Bisphosphonates have been shown to prevent or delay bone destruction and related pain in clinical trials involving patients with bone metastases related to:

How Can Osteoporosis be Treated and/or Prevented?

Osteoporosis is a weakening of the bones related to aging and other factors. Although there is no cure for osteoporosis, a number of medications have been approved by the FDA to prevent and/or treat osteoporosis in postmenopausal women.

  • Bisphosphonate drugs
  • Miacalcin®
  • Forteo® (teriparatide)
  • Evista® (raloxifene)
  • Hormone Replacement Therapy (HRT)

Bisphosphonate Drugs: Bisphosphonate drugs treat osteoporosis by decreasing the rate of bone resorption. Resorption is an activity that takes place in normal bone remodeling. In osteoporosis, resorption occurs faster than new bone formation.

Fosamax® is approved as a treatment for osteoporosis in men and is approved for treatment of glucocorticoid (steroid)-induced osteoporosis in men and women. Actonel® is approved for prevention and treatment of glucocorticoid-induced osteoporosis in men and women.

Boniva® (ibandronate) is approved for the treatment and prevention of osteoporosis in postmenopausal women. Boniva® is available for oral (by mouth) administration

Miacalcin® (calcitonin): Calcitonin is a natural hormone that increases the deposition of calcium in the bones. Calcitonin is the active ingredient in Miacalcin®, which has been shown to prevent bone loss in postmenopausal women with reduced bone mass.6

Forteo® (teriparatide): Forteo® is a form of parathyroid hormone that increases bone formation. It is approved for the treatment of osteoporosis. Forteo® is approved for the treatment of osteoporosis in men and postmenopausal women who are at high risk for a fracture.

Evista® (raloxifene): Evista® is a type of hormonal therapy called a selective estrogen receptor modulator (SERM). It is approved for the prevention of osteoporosis in postmenopausal women and has been evaluated in the prevention of breast cancer.

Hormone Replacement Therapy (HRT): HRT has been shown to prevent bone loss in postmenopausal women. Examples of HRT include:

  • Estrogens (brand names, such as Climara®, Estrace®, Estraderm®, Estratab®, Menostar, Ogen®, Ortho-Est®, Premarin®, Vivelle®, and others)
  • Estrogens and Progestins (brand names, such as Activella, FemHrt®, Premphase®, Prempro®, and others)

References


1 Sverrisdottir A, Fornander T, Jacobsson H, et al. Bone mineral density among premenopausal women with early breast cancer in a randomized trial of adjuvant endocrine therapy. J Clin Oncol. 2004 Sep 15;22(18):3694-9.

2 Eriksson S, Eriksson A, Stege R et al. Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens. Calcif Tissue Int. 1995;57:97–99.

3 Shapiro CL, Manola J, Leboff M. Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol. 2001;19:3306–3311.

4 Saarto T, Blomqvist C, Valimaki M et al. Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol. 1997;15:1341–1347.

5 Ross JR, Saunders Y, Edmonds PM, et al. Systematic Review of Role of Bisphosphonates on Skeletal Morbidity in Metastatic Cancer. British Medical Journal 2003; 327:469-471.

6 Ellerington MC; Hillard TC; Whitcroft SI, et al. Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis. Calcif Tissue Int. 1996 Jul;59(1):6-11.

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