Osteoporosis is a progressive metabolic bone disease that decreases bone density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures with minor or inapparent trauma, particularly in the thoracic and lumbar spine, wrist, and hip (called fragility fractures). Diagnosis is by dual-energy x-ray absorptiometry (DEXA scan) or by confirmation of a fragility fracture. Prevention and treatment involve risk factor modification, Ca and vitamin D supplements, exercises to maximize bone and muscle strength and minimize the risk of falls, and drug therapy to preserve bone mass or stimulate new bone formation.
Bone is continually being formed and resorbed. Normally, bone formation and resorption are closely balanced. Osteoblasts (cells that make the organic matrix of bone and then mineralize bone) and osteoclasts (cells that resorb bone) are regulated by parathyroid hormone (PTH), calcitonin, estrogen, vitamin D, various cytokines, and other local factors such as prostaglandins.
Peak bone mass in men and women occurs by the mid 20s. Men have higher bone mass than women. After achieving peak, bone mass plateaus for about 10 yr, during which time bone formation approximately equals bone resorption. After this, bone loss occurs at a rate of about 0.3 to 0.5%/yr. Beginning with menopause, bone loss accelerates in women to about 3 to 5%/yr for about 5 to 7 yr and then the rate of loss decelerates.
Osteoporotic bone loss affects cortical and trabecular (cancellous) bone. Loss of both types contributes to skeletal fragility and fractures.
Because stress, including weight bearing, is necessary for bone growth, immobilization or extended sedentary periods result in bone loss. A low body mass index predisposes to decreased bone mass. Certain ethnicities, including whites and Asians, have a higher risk of osteoporosis. Insufficient dietary intake of Ca, P, Mg, and vitamin D predisposes to bone loss, as does endogenous acidosis. Tobacco and alcohol use also adversely affect bone mass. A family history of osteoporosis, particularly a parental history of hip fracture, also increases risk.
Symptoms and Signs
Patients with osteoporosis are asymptomatic unless a fracture has occurred. Nonvertebral fractures are typically symptomatic, but about two thirds of vertebral compression fractures are asymptomatic. A vertebral compression fracture that is symptomatic begins with acute onset of pain that usually does not radiate, is aggravated by weight bearing, may be accompanied by point spinal tenderness, and typically begins to subside in 1 wk. However, residual pain may last for months or be constant.
Multiple thoracic compression fractures eventually cause dorsal kyphosis, with exaggerated cervical lordosis (dowager's hump). Abnormal stress on the spinal muscles and ligaments may cause chronic, dull, aching pain, particularly in the lower back.
• Dual-energy x-ray absorptiometry (DEXA)
Bone density should be measured using DEXA to screen people at risk and to follow patients with documented low bone density, including those undergoing treatment.
Typically, DEXA is done in all women ≥ 65 yr, women between menopause and 65 who have risk factors, including a family history of osteoporosis, a low body mass index (eg, previously defined as body weight < 127 lb), and use of tobacco and/or drugs with a high risk of bone loss (eg, glucocorticoids). DEXA is also recommended for both men and women of any age who have had fragility fractures, older adults with unexplained sudden onset of back pain, patients with decreased bone density or asymptomatic vertebral compression fractures incidentally noted on imaging studies.
Bone density measurement: DEXA is used to measure bone mineral density (g/cm2); it is suggestive of osteopenia or osteoporosis (in the absence of osteomalacia), predicts the risk of fracture, and can be used to follow treatment response. Bone density is ideally measured at three sites, including the lumbar spine and both hips.
DEXA results are reported as T-scores and Z-scores. The T-score corresponds to the number of standard deviations that the patient's bone density differs from the peak bone mass of a healthy, young person of the same sex and ethnicity. The WHO establishes cutoff values for T-scores that define osteopenia and osteoporosis. A T-score < -1.0 and > -2.5 defines osteopenia. A T-score ≤ -2.5 suggests osteoporosis.
The Z-score corresponds to the number of standard deviations that the patient's bone mineral density differs from that of a person of the same age and sex and should be used for children, premenopausal women, or men < 50 yr. If the Z-score is ≤ -2.0, bone density is low for the patient's age and secondary causes of bone loss should be considered.
In patients being treated for osteoporosis, DEXA should be repeated, usually about every 2 yr, but sometimes more frequently in patients taking glucocorticoids. Patients with as significantly decreased bone mineral density should be evaluated for drug adherence and secondary causes of bone loss.
• Risk factor modification
• Ca and vitamin D supplements
• Antiresorptive drugs (eg, bisphosphonates, hormone replacement therapy)
The goals of treatment are to preserve bone mass, prevent fractures, decrease pain, and maintain function.
Risk factor modification can include increasing weight-bearing exercise, minimizing caffeine and alcohol intake, and smoking cessation. The optimal amount of weight-bearing exercise is not established, but an average of 30 min/day is recommended.
All men and women should consume at least 1000 mg of elemental Ca daily. An intake of 1200 to 1500 mg/day (including dietary consumption) is recommended for postmenopausal women and older men and for periods of increased requirements, such as pubertal growth, pregnancy, and lactation. Diet alone is rarely adequate; Ca supplements are needed, most commonly as Ca carbonate or Ca citrate. Ca should be taken in divided doses of 500 to 600 mg bid or tid.
Vitamin D supplementation is recommended with 800 to 1000 IU/day. Patients with vitamin D deficiency may need even higher doses. Supplemental vitamin D is usually given as cholecalciferol, the natural form of vitamin D, although ergocalciferol, the synthetic plant-derived form, is probably also acceptable. The 25-hydroxy vitamin D level should be ≥ 30 ng/mL.
Bisphosphonates are first-line drug therapy. By inhibiting bone resorption, bisphosphonates preserve bone mass and can decrease vertebral and hip fractures by 50%. They can be given orally or IV. Oral bisphosphonates include alendronate (10 mg once/day or 70 mg once/wk) and risedronate (5 mg once/day, 35 mg once/wk, or 150 mg once/mo). Zoledronic acid is given IV (5 mg once/yr). Ibandronate can be given orally (150 mg once monthly) or IV (3 mg once every 3 mo). Oral bisphosphonates must be taken on an empty stomach with a full (8-oz, 250 mL) glass of water, and the patient must remain upright for at least 30 min (60 min for ibandronate).
Estrogen can preserve bone density and prevent fractures. Most effective if started within 4 to 6 yr of menopause, estrogen may slow bone loss and possibly reduce fractures even when started much later. Use of estrogen increases the risk of thromboembolism and endometrial cancer and may increase the risk of breast cancer. The risk of endometrial cancer can be reduced in women with an intact uterus by taking a progestin with estrogen.
A 67-year-old woman comes to your office because she is concerned about osteoporosis. She went through menopause at 56, has no history of bone fractures, no smoking history, and no known family history of hip fractures. Her weight is 51 kg and height is 60 cm. Physical examination is unremarkable. A dual X-ray absorptiometry shows: Average Z-score= -1.6 SD, Average T-score= -0.9 SD. Now that you have completed a basic screening for osteoporosis, your patient returns to your office for an interpretation of her tests results. At this time, it is most appropriate to inform the patient that:
A. Because of her risk factors, treatment with calcium and alendronate should be initiated
B. Because of her risk factors, treatment with calcium should be initiated
C. Compared to aged matched controls, her bone density is 0.9 SDs below the mean
D. Compared to healthy young adults, her bone density is 1.6 SDs below the mean
The correct answer is B. All individuals should ensure that they consume adequate amounts of calcium. Premenopausal, non-pregnant women should consume about 1,000 mg/day of calcium. Postmenopausal women should consume 1,200-1,500 mg/day of calcium and pregnant women should consume about 1,300 mg/day of calcium.
Treatment with alendronate (choice A) or any other approved osteoporosis medication should generally be reserved for the following women with post menopausal osteoporosis: women who suffered low impact trauma, women with T-Scores < 2.5, women with T-scores < 1.5 and risk factors, and women who continue to lose bone mass despite preventive intervention.
Compared to aged matched controls, her bone density is 0.9 standard deviations below the mean (choice C) and compared to healthy young adults, her bone density is 1.6 standard deviations below the mean (choice D) are incorrect interpretations of BMD. A patient's T-score compares women to healthy young adults. It is used to make the diagnosis of osteoporosis. T-scores between 1 and 2.5 SD below the mean are defined as osteopenia. A t-score of less than 2.5 SD below the mean defines osteoporosis. The Z-score compares BMD of age and race matched controls. A low Z-score (<-2.0 SD below the mean) may be consistent with secondary cause of osteoporosis (e.g., hyperthyroidism or hyperparathyroidism).
A 17-year-old female comes to your office with an 8-month history of amenorrhea. Menarche occurred at age 12 and her menses were regular until the past year. The patient’s vital signs are in the normal range for her age except for a BMI of 16.1 kg/m2 (below the third percentile for age). She practices dance several hours a day and works out regularly. She admits that she follows a strict 800-calorie/day diet to keep in shape for ballet. You order a CBC, a complete metabolic profile, a urine Beta-hCG level, FSH and LH levels, and a TSH level. Which one of the following is also recommended as part of the workup?
A. An EKG
B. Pelvic ultrasonography
C. Abdominal/pelvic CT
D. A DEXA scan
ANSWER: D. The female athlete triad is a relatively common condition in athletes, and is characterized by amenorrhea, disordered eating, and osteoporosis. It is more common in sports that promote lean body mass. Female athletes should be screened for the disorder during their preparticipation evaluations. Individuals who present with one or more components of the triad should be evaluated for the other components. This patient evidences disordered eating (low BMI for age) and secondary amenorrhea, and should be screened for osteoporosis using a DEXA scan. The International Society for Clinical Densitometry recommends using the Z-score, rather than the T-score, when screening children or premenopausal women. The T-score is based on a comparison to a young adult at peak bone density, whereas the Z-score uses a comparison to persons of the same age as the patient. A Z-score less than –2.0 indicates osteoporosis.
An EKG is not required in this patient since she has normal vital signs. Pelvic ultrasonography is not necessary unless an abnormal finding is identified on a pelvic examination. Abdominopelvic CT would be inappropriate given the patient’s age and lack of abdominopelvic symptoms such as pain or a mass.
A 55-year-old woman comes to the office for a periodic health maintenance examination. Her review of systems is positive for fatigue, recent weight gain, temperature intolerance with hot flashes being frequent, and some mild pruritus over her hands. Her last menstrual period was seven months prior. She smokes one-half pack of cigarettes per day. She appears her stated age, is well and in no distress. Her temperature is 37.0 C (98.6 F), blood pressure is 110/80 mm Hg, and pulse is 65/min. Physical examination is unremarkable. Concerning her post-menopausal status, the most appropriate intervention to reduce long-term morbidity and mortality is
A. annual bone density surveys
B. estrogen and progesterone replacement
C. estrogen and progesterone replacement and bisphosphonate therapy
D. estrogen replacement and bisphosphonate therapy
The correct answer is C. This patient is postmenopausal and not on hormone replacement therapy (HRT). Accelerated bone loss and osteoporosis are top among the increased risks that such women have. Bisphosphonates are a class of drugs that are taken orally and act to inhibit osteoblast formation and/or function. Their precise mechanism(s) of action are unknown. This, in addition to estrogen and progesterone replacement will reduce her long-term morbidity and mortality.
Annual bone density surveys (choice A) are a monitoring tool. These tests are not therapeutic in any way and in order to reduce long-term morbidity, some intervention is required. Bone density surveys are the standard monitoring tool for following the progression of osteoporosis.
It is appropriate to treat with estrogen and progesterone replacement (choice B) together since the progesterone offsets the unopposed estrogen. However bisphosphonate therapy is absent from this regimen.
Because the beneficial effects of progesterone on estrogen action is lost with estrogen replacement and bisphosphonate therapy (choice D) alone, it is incorrect.
A 58-year-old woman comes to the office for a periodic health maintenance examination. You notice in her chart that her last menstrual period was two years ago, and at that time, she was not interested in discussing hormone replacement therapy. Now she says that she has noticed that a few of her friends have been "shrinking" and she is ready to take something "for osteoporosis." She read that women with thromboembolic disease should not take estrogen. She vaguely remembers having a few "blood clots" many years ago. Dual energy absorptiometry (DEXA) shows a bone mineral density that is more than 2.5 standard deviations below the mean. Alendronate is prescribed. The patient should be advised to
A. avoid weight-bearing exercise
B. return to the office in one week for a complete blood count (CBC)
C. take the alendronate, along with calcium, after breakfast
D. take the alendronate first thing in the morning, on an empty stomach, with a full glass of water, and remain upright for at least 30 minutes
The correct answer is D. Alendronate (Fosamax), is a biphosphate that is used to treat and prevent osteoporosis. Because esophageal irritation and ulceration are side effects, it is necessary to advise patients that after taking the pill, they must remain sitting upright or standing for at least 30 minutes. Also, it must be taken with a full glass of water on an empty stomach because it may interact with other substances. Alendronate works by reducing the activity of osteoclasts, which decreases the rate of bone loss and increases the amount of mineral density.
It would be incorrect to advise this patient to avoid weight-bearing exercise (choice A). It is actually important to advise the patient to engage in weight-bearing exercise to help maintain bone density.
It is not necessary for the patient to return to the office in one week for a complete blood count (CBC), (choice B). Common side effects of alendronate are esophagitis, gastrointestinal upset, headache, bone and joint pain, a rash, and an altered sense of taste. Agranulocytosis, which is a rare side effect of the antipsychotic agent clozapine, is not typically associated with alendronate. Therefore, regular monitoring of the CBC is unnecessary.