Causes and Risk Factors of Osteoporosis



Fig. 1
Mean BMD at the femoral neck by age in the United States, WM white males, WF white females, BM black males, BF black females (Source: Data from Looker AC)




Pathophysiology


Osteoporosis is caused by the excessive breakdown of bone structure, inadequate bone formation, or an imbalance in the activity between the bone cells responsible for bone remodeling. It results from the increased number or activity of osteoclasts, the cells of bone resorption; the decreased number or activity of osteoblasts, the cells of bone formation; or areas of bone that demonstrate both of these abnormal bone cell characteristics [3]. Osteoporosis is evaluated by a bone mineral density (BMD) test which measures the amount of mineral per square centimeter and can be performed by a number of radiological densitometry procedures, most often dual energy x-ray absorptiometry (DXA) [4]. The most common areas evaluated are the lumbar spine or proximal hip and distal radius. With osteoporosis, bone mineral density is decreased due to the breakdown of bone without compensatory, subsequent remodeling [5].

Compromised bone density results in decreased ability to withstand trauma. Bone loss can accelerate rapidly in certain conditions of high bone turnover such as menopause when estrogen levels fall sharply, neoplasia, metabolic abnormalities, or sudden immobility such as spinal cord injury (SCI) [6]. Bone fractures may occur with minimal external trauma forces such as a mechanical fall or internal trauma resulting from the force of a cough or sneeze. Due to weakened microarchitecture of bone and normal forces of gravity and routine, daily activities can result in spontaneous fractures, particularly in vulnerable populations.

The anatomical characteristics of bone in certain regions of the body can cause increased susceptibility to damage from osteoporosis. Although 80 % of the total skeleton is comprised of densely packed cortical bone, this type of bone is principally found in outer layers of long bones of the appendicular skeleton and is designed for structural support. Cortical bone has low bone turnover rates and is thus less likely to fracture than trabecular bone [7]. Characterized by increased porosity and reduced tensile strength, trabecular bone is heavily concentrated in the axial skeleton of the spine and is constantly being shaped and remodeled. Both the appendicular and axial skeleton are at risk of a fracture after a fall or other sustained trauma [7].


Epidemiology


Osteoporosis has generally been divided into two categories: primary and secondary osteoporosis. Primary osteoporosis is age related, affects 95 % of women and about 80 % of men, and is related to estrogen loss in women and a testosterone deficiency in men; other factors include low calcium and vitamin D intake as well as hyperparathyroidism. In contrast, secondary osteoporosis stems from other conditions including hormonal imbalances, diseases, and medications that predispose to bone loss. It may arise at any age and affects both men and women [8]. The risk of osteoporosis and its severity is influenced by a variety of controllable and uncontrollable factors. Controllable factors include dietary deficiencies in vitamin D and calcium and in certain fruits and vegetables that enhance calcium absorption by limiting urinary excretion of calcium; in contrast, diets high in animal protein or sodium favor calciuria or bodily elimination of calcium through urine. Vitamin D is essential for calcium absorption which, if impaired, leads to an increase in parathyroid hormone (PTH) produced by the parathyroid glands. If calcium levels are low, these glands, the most important regulators of calcium levels in the blood, respond by secreting more PTH, resulting in increased calcium levels which, in turn, trigger bone resorption [9]. Other controllable factors range from high caffeine intake and an inactive lifestyle to smoking, alcohol consumption, and intentional weight loss beyond one’s ideal body weight or implemented at the expense of overall nutritional status [1, 6]. Uncontrollable risk factors include age greater than 75 years old, female gender, postmenopausal status, family history of osteoporosis, and low body weight, thin build, or sudden unintentional weight loss from illness [1, 6].

Gender differences can affect the prevalence and severity of osteoporosis. Beginning at age 40, both sexes lose axial bone mass at relatively slow rates, but women lose bone mass more rapidly because of the onset of menopause in the late 40s or early 50s, contributing to increased risk of fracture to the axial skeleton. For men, who do not experience the sudden loss of gonadal sex steroid secretion, the reduction of reproductive hormones is more gradual, and bone loss occurs at a slower rate [10] (Table 1).


Table 1
Risk factors in the development of osteoporosis


































Controllable

Uncontrollable

Inadequate dietary calcium or vitamin D

Age >75 years

Inadequate fruit and vegetable consumption

Female

Excessive protein, sodium, or phosphorous intake

Postmenopausal

Sedentary lifestyle

Family history

Ethyl alcohol (EtOH)

Low body weight/thin build

Smoking

Genetics

Weight loss

Hormonal levels (may be controlled with medications if diagnosed)

Medications

Environment with low sunlight


Medications Leading to Osteoporosis


Several medications have been shown to contribute to the development of osteoporosis. Glucocorticoids (aka corticosteroids), the leading secondary cause of osteoporosis, decrease bone formation by downregulating osteoblasts and prolonging their life span [11]. In addition, an inhibitory effect on sex hormones influences bone formation. When used chronically in high doses, glucocorticoids restrict intestinal vitamin D-dependent calcium absorption, increase calcium excretion, and can cause osteomalacia, a softening of bone generally caused by vitamin D deficiency.

Thiazolidinediones given to persons with diabetes mellitus can lead to osteoporosis by their direct action on bone cell differentiation. A Diabetes Outcome Progression Trial (ADOPT) found that patients randomized to rosiglitazone have a higher risk of fractures than those receiving metformin or glyburide [12, 13].

Unfractionated heparin given for greater than one year has been associated with decreased bone formation and increased resorption, but the effects are notably less with low molecular weight heparin [14]. Proton pump inhibitors moderately impede the calcium resorption essential to bone formation; some studies show that H2 blockers have a smaller adverse effect, yet others report a neutral effect [11]. Significant doses of thyroxine suppress thyroid-stimulating hormone (TSH) causing bone loss. Vitamin A (greater than10,000 units/day) and vitamin D (greater than 2,000 units/day) have a similar effect.

Immune modulating drugs can also lead to decreases in BMD. Methotrexate decreases osteoblast activity and bone resorption in a dose-dependent manner. Calmodulin–calcineurin phosphatase inhibitors, used for immunosuppression post organ transplants, have been implicated in osteoporosis because they increase bone turnover; however the exact mechanism is unknown. Their effect is further complicated because they are often used concurrently with glucocorticoids [15, 16]. Long-term use of the antiepileptic drugs (AEDs) carbamazepine, phenobarbital, phenytoin, and valproic acid have been associated with decreased BMD due to elevated vitamin D catabolism, elevated parathyroid hormone, or increased osteoclastic activity [17, 18]. Increasing evidence points to a negative association between antidepressant drugs, particularly selective serotonin reuptake inhibitors (SSRIs), and low bone density coupled with fracture risk. A study of 5,008 adults over the age of 50, conducted by the Canadian Multicentre Osteoporosis Research Group, found that patients taking SSRIs on a daily basis experienced an increased risk of fragility fracture, increased chance of falling, and lower BMD at the hip and spine than those not taking the drugs [19].


Fractures


Statistics show that approximately 50 % of women and 25 % of men will break a bone due to osteoporosis [20]. Worldwide, it is estimated that there are 8.9 million fractures annually, resulting in an osteoporotic fracture every three seconds [21]. A prior fracture is associated with an 86 % increased risk of any future fracture [22]. A 10 % loss of bone mass in the vertebrae can double the risk of vertebral fractures; similarly, a 10 % loss of bone mass in the hip can result in a 2.5 times greater risk of hip fracture [23].

By 2050, the worldwide incidence of hip fracture is projected to increase 310 % in men and 240 % in women, as a result of longer life spans in the developed and developing world [20]. The number of patients hospitalized due to an osteoporotic complication is comparable to the number hospitalized for hypertensive-related heart disease, and the disease causes greater disability than that caused by cancer.


Vertebral Compression Fractures


Vertical compression fractures occur when trauma causes the vertebra in the spine to compress and eventually collapse. Unlike most spine fractures of a traumatic nature, individuals with vertebral compression fractures may present without complaints of pain; indeed, approximately two-thirds of vertebral compression fractures are painless [24]. Regardless of pain intensity, if a vertebral fracture goes unrecognized, it can result in cumulative damage including further breakdown of bone structure, producing loss of vertebral height, increased curving of the spine leading to a “hunchback” deformity (spinal thoracic kyphosis, Fig. 2), and spinal cord compression. Vertebral fractures most often occur in the lower thoracic and upper lumbar portions of the spine because of the higher proportion of trabecular bone to cortical bone [25].

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Fig. 2
Image showing a normal and kyphotic spine (Source: Used with permission from Mayo Clinic Foundation for Education and Research)

Clinical consequences of an osteoporotic compression fracture range from mild to severe. Significant kyphoscoliosis, a combination of outward curvature (kyphosis) and lateral curvature (scoliosis) of the spine, can lead to decreased pulmonary function from reduced lung surface area [26] or altered sitting or standing posture, resulting in compromised thoracic expansion. Larger fractures in the spine can progress to spinal instability through angulation of the vertebral column. If such changes compromise the spinal canal, cord compression can be observed, creating an urgent need for surgical decompression to avert devastating neurological consequences, including motor or sensory loss [26].

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Aug 17, 2017 | Posted by in PHYSICAL MEDICINE & REHABILITATION | Comments Off on Causes and Risk Factors of Osteoporosis
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