Secondary Osteoporosis: Other Causes of a Decrease in Bone Density

By: 
Shira R. Saul, MD and Yan Yan Sally Xie MD

Most people recognize osteoporosis as a disease in which problems within the body’s skeleton cause it to weaken and fracture with very little trauma, particularly as part of the aging process. This is known as primary osteoporosis, which is responsible for 8.9 million fractures worldwide each year. In the U.S. alone, it’s estimated to affect 10 million Americans, with an additional 34 million diagnosed with low bone mass.

There is, however, evidence of an increase in both men and pre-menopausal women of secondary osteoporosis, a condition in which certain medical conditions or treatments interfere with the attainment of peak bone mass and may cause bone loss. The focus of this article to is to review its most common endocrine causes.

The mechanism of osteoporosis

Bones are dynamic, living organs with multiple functions. Besides skeletal formation, bones are involved in mineral regulation, acid-base status, (the balance between acidity and alkalinity compounds in the blood, which it needs to function properly), and the production of platelets, red blood cells and white blood cells.

Due to constant mechanical stress, bones are frequently breaking down and rebuilding. This normal process is called remodeling. Osteoporosis occurs when there is a mismatch in bone turnover and typically involves more rapid bone breakdown than normal due to the action of osteoclasts (a large bone cell that breaks down bone tissue and is responsible for bone resorption) versus the action of bone buildup created by osteoblasts (a cell that makes bone).

There are two types of bone: cortical (kōr’ti-kăl) and cancellous (kan’sĕ-lŭs—denoting bone that has a lattice-like or spongy structure). Cortical bone makes up the outer layer of the bone structure while cancellous bone fills the inside portion. Although most bones are a mix of cortical and cancellous bone, some have a higher percentage of one type. For example, the spine is composed mainly of cancellous bone, the forearm is mainly cortical and the hip is comprised of both types. This is important because secondary causes of osteoporosis affect bone remodeling differently and, therefore, may have different treatment modalities.

Endocrine Gastrointestinal Hematologic Rheumatologic Medications Miscellaneous
Hyperthyroidism Celiac disease Leukemia, lymphoma Rheumatoid arthritis Excess
glucocorticoids
HIV/AIDS
Hyperparathyroidism Crohn’s disease Multiple myeloma Systemic lupus
erythematous
Excessive thyroid hormone Transplant
Hypercortisolism Ulcerative colitis Mastocytosis Multiple sclerosis Proton pump inhibitors Immobilization
Diabetes Mellitus Gastric bypass   Ankylosing
spondylitis
Selective serotonin uptake inhibitors Pregnancy
Hypogonadism       Seizure medications Anorexia
Vitamin D deficiency       Progesterone  
        Heparin  
        Thiazolidinediones  
        Chemotherapy  

Secondary causes of osteoporosis

Secondary causes of osteoporosis can be divided into several categories: endocrine, gastrointestinal, hematologic, rheumatologic, medications and miscellaneous. The chart above includes a list of common conditions known to cause secondary osteoporosis. This article will further address the endocrine system category.

Hyperthyroidism

Hyperthyroidism is a condition in which the thyroid gland is overactive and produces excessive thyroid hormone. Symptoms may include weight loss, rapid or irregular heartbeat, sweating and irritability. Excess thyroid hormone may be due to a single overactive nodule, known as a toxic adenoma, multiple overactive nodules, known as toxic multi-nodular goiter, or autoimmune gland stimulation known as Graves’ disease. Thyroid hormone affects both bone buildup and breakdown, with excess hormone resulting in more bone breakdown, bone weakening and subsequent fractures.

Hyperparathyroidism

Hyperparathyroidism results in excessive parathyroid hormone. This may be caused by an overactive single parathyroid gland, commonly called primary hyperparathyroidism, or from secondary causes such as vitamin D deficiency, which may stimulate all four parathyroid glands. Parathyroid glands are small glands of the endocrine system, located in the neck behind the thyroid, that regulate the amount of calcium, which is used to control many systems in the body. Parathyroid hormone released by the glands regulates calcium, phosphorus and vitamin D. In a healthy individual without kidney disease, high levels of parathyroid hormone will increase the active form of vitamin D, increase calcium absorption from the gut and kidney, and cause phosphorus excretion in the urine. In addition, parathyroid hormone will actively break down cortical bone, found mainly in the forearm and femoral neck (hip), thus weakening them and predisposing a person to fractures. If primary hyperparathyroidism is suspected, your doctor may order additional images of the forearm.

Hypercortisolism

Cortisol is a hormone made in the adrenal glands, which are located on the top of the kidneys, and is released in times of stress. Excessive cortisol can result when the adrenal glands synthesize excessive cortisol in a condition known as Cushing’s syndrome, or when one takes oral steroids (i.e., hydrocortisone, prednisone, or dexamethasone) for an extended period of time. Both conditions result in weakening of the bones – cancellous bone more so than cortical bone – and may lead to spinal vertebral fractures. Depending on your underlying condition, your physician may order an additional imaging test called a Vertebral Fracture Assessment (VFA) to specifically examine your spine.

Diabetes mellitus

Both type 1 and type 2 diabetes ultimately lead to a decrease in insulin production by the pancreas. Type 1 diabetes is typically found in younger, leaner patients and is due to autoimmune destruction of the pancreas, whereas type 2 diabetes is often seen in older, overweight individuals and thought to be due to pancreas burnout accompanied by insulin resistance, a condition in which the body’s cells don’t respond normally to insulin, thus preventing glucose (blood sugar) from entering the body’s cells. Insulin, as well as another pancreatic hormone called amylin, may be important in bone formation. Hence, the lack of insulin may contribute to low bone mineral density and increased fracture risk. Additionally, uncontrolled diabetes results in vision impairment and nerve damage in the feet, which may predispose patients to fall. Furthermore, the use of certain antidiabetic medications has been shown to increase fractures in postmenopausal women.

Hypogonadism

Estrogen and testosterone, sex hormones found in both women and men, are crucial in bone health, with estrogen thought to be the key hormone. Estrogen is formed from testosterone and is found in both women and men, although women have higher levels of the hormone. Estrogen works by promoting osteoblasts and, thus, bone formation. It also inhibits osteoclasts, preventing bone breakdown. Common causes of low sex hormones may include aging and medications as well as thyroid dysfunction, pituitary disease, diabetes and obesity. In both women and men, if either the ovaries or testicles fail to produce sex hormones, bone loss may result. In women below 40 years of age, this is called primary ovarian failure and is usually treated with estrogen replacement therapy.

Vitamin D Deficiency

Vitamin D is a fat-soluble vitamin that enhances calcium absorption in the gut and maintains adequate calcium and phosphate levels in the blood, both which are needed for bone mineralization. Without sufficient vitamin D, bones may weaken. This condition is known as osteomalacia in adults and rickets in children. Parathyroid hormone, discussed earlier, may also increase with low levels of vitamin D, thus worsening bone breakdown.

Vitamin D deficiency with or without calcium deficiency has been associated with several gastrointestinal malabsorptive disorders (malabsorption is abnormality in absorption of food). These include celiac disease, inflammatory bowel diseases such as Crohn’s and ulcerative colitis, and certain gastric bypass surgeries.

Evaluation and treatment of osteoporosis

The diagnosis of osteoporosis is made either by imaging, typically with dual-energy x-ray absorptiometry (DEXA) without vertebral fracture assessment (VFA), or by a non-traumatic vertebral fracture. It is universally accepted that all women over 65 should be screened for osteoporosis. For men and women younger than 65 with secondary causes of osteoporosis, screening guidelines vary by medical society.

A laboratory evaluation may include a complete blood count, complete metabolic panel (specifically kidney and liver functions, calcium, magnesium and phosphorus), thyroid function tests, vitamin D levels, parathyroid hormone, testosterone, 24-hour urine for calcium and cortisol, tissue transglutaminase and serum/urine protein electrophoresis.

In most cases, treatment of secondary osteoporosis involves targeting the underlying cause. For example, if someone has a parathyroid adenoma (non-cancerous tumor) that is producing excess parathyroid hormone, the treatment is either surgery or medicine, depending on other risk factors. The exception to this is a patient who requires long-term glucocorticoids, typically defined as prednisone 5 milligrams daily for three months. In these patients, some organizations recommend preventive treatment with a bisphosphonate, a class of drugs that prevent the loss of bone mass.

Regardless of the underlying cause, most patients with secondary osteoporosis are advised to consume adequate vitamin D and calcium (amounts vary depending on age and sex) and to perform weight-bearing exercises. Other treatment options include medications such as bisphosphonates or a daily injection that promotes bone formation, known as teriparatide. Follow-up labs tests and imaging will depend on the disease’s cause, severity and treatment.

The bottom line: Heightened awareness of the potential presence of secondary osteoporosis and increased vigilance for its detection are essential in improving bone health in these patients.

For additional information, visit: http://www.empoweryourhealth.org/endocrine-conditions/osteoporosis.