Osteoporosis is characterized by the imbalance between the activity of the osteoblasts, the bone forming cells, and the osteoclasts, the cells that resorb the bone tissue, imbalance that favors the osteoclasts.1


Primary osteoporosis, the most common form of the disease, occurs in people from 51 to 65 years of age with a female-to-male ratio of 6:1.

Primary osteoporosis can be further subdivided into two types. Type I, postmenopausal osteoporosis, results from decreased circulating levels of estrogen. It is seen in postmenopausal women and affects the majority of persons older than 70 years. Bone loss is rapid. There is swift trabecular bone loss up to 8% per year. Type I osteoporosis causes primarily trabecular bone loss with only 0.5% cortical bone loss per year. Fractures occur in locations of trabecular bone loss such as the distal radius and vertebrae. The cause of primary osteoporosis is a changing hormonal milieu.

Type II, senile osteoporosis, is a consequence of aging. It causes a more global bone loss affecting cortical and cancellous bone such as in the femoral neck. Type II osteoporosis is seen in persons older than 70 years. The female-to-male ratio is 2:1. The bone loss occurs in both the trabecular and cortical bone and averages 0.3–0.5% per year. Fractures occurring as the result of type II osteoporosis typically involve the hip, pelvis, humerus, tibia, and vertebral bodies. The causes of senile osteoporosis are those seen with aging and include calcium deficiency, decreased vitamin D, and increased parathormone activity.

Secondary Osteoporosis

Secondary osteoporosis results from a variety of causes. The most common are chronic or prolonged corticosteroid use and endocrine disorders. The endocrine disorders associated with osteoporosis are hyperthyroidism, hyperparathyroidism, diabetes, Cushing disease, and euplastic disorders.






Osteoporosis is a public health problem affecting more than 40 million people, one-third of postmenopausal women and a substantial portion of the elderly in the United States and almost as many in Europe and Japan

Restoration of bone is difficult. It is therefore imperative to maximize peak bone mass during skeletal growth and then to maintain it during maturity. This requires adequate dietary calcium and vitamin D intake.

The recommended amounts for adults are 1200 mg/day of calcium and 400 mg of vitamin D. For postmenopausal women, 1500 mg/day of calcium is recommended.

Impact exercise is effective in maintaining bone mass. It is also important to avoid those factors that promote osteoporosis such as the use of tobacco products and excessive alcohol consumption.


  • Advise smoking cessation and alcohol moderation (≤2 drinks per day). (why???????)

  • –Advise 1500-mg elemental calcium daily for established osteoporosis, glucocorticoid therapy, or age >65 y.1

  • –Assess for vitamin D deficiency with a 25-hydroxy vitamin D level

    • Treat vitamin D deficiency if present.

  • –Treatment of osteoporosis

    • Bisphosphonate therapy

    • Consider estrogen therapy in menopausal women <50 y of age

    • Consider parathyroid hormone in women with very high risk for fracture

  • –Fall prevention program

    • Home safety evaluation

    • Avoid medications that can cause sedation, orthostatic hypotension, or affect balance

    • Assistive walking devices as necessary



  • –All patients should have serial heights and observed for kyphosis.

  • –Obtain a lateral vertebral assessment with DXA scan or x-ray if height loss exceeds 4 cm.

  • –DXA bone mineral densitometry should be repeated no more than every 12–24 mo.


  • –Postmenopausal women


▶ NAMS 2010, AACE 2010, ACOG 2012

  1. Recommend maintaining a healthy weight, eating a balanced diet, avoiding excessive alcohol intake, avoiding cigarette smoking, and utilizing measures to avoid falls.

  2. Recommend supplemental calcium 1200 mg/d and vitamin D3 800–1000 international units (IU)/d.

  3. Recommend an annual check of height and weight, and assess for chronic back pain.

  4. DXA of the hip, femoral neck, and lumbar spine should be measured in women age ≥65 y or postmenopausal women with a risk factor for osteoporosis.a

  5. Recommend repeat DXA testing every 1–2 y for women taking therapy for osteoporosis and every 2–5 y for untreated postmenopausal women.

  6. Recommend against measurement of biochemical markers of bone turnover.

  7. Recommend drug therapy for osteoporosis for:

    1. Osteoporotic vertebral or hip fracture

    2. DXA with T score ≤ –2.5

    3. DXA with T score ≤ –1 to –2.4 and a 10-y risk of major osteoporotic fracture of ≥20% or hip fracture ≥3% based on FRAX calculator, available at http://www.shef.ac.uk/FRAX/

  8. Consider the use of hip protectors in women at high risk of falling.



  1. Options for osteoporosis drug therapy:

    1. Bisphosphonates

      1. First-line therapy

      2. Options include alendronate, ibandronate, risedronate, or zoledronic acid

      3. Potential risk for jaw osteonecrosis

    2. Denosumab

      1. Consider for women at high fracture risk

    3. Raloxifene

      1. Second-line agent in younger women with osteoporosis

    4. Teriparatide is an option for high fracture risk when bisphosphonates have failed

      1. Therapy should not exceed 24 months

    5. Calcitonin

      1. Third-line therapy for osteoporosis

      2. May be used for bone pain from acute vertebral compression fractures.

  2. Vitamin D therapy should maintain a 25-OH vitamin D level between 30 and 60 ng/mL.

aPrevious fracture after menopause, weight <127 lb, BMI <21 kg/m2, parent with a history of hip fracture, current smoker, rheumatoid arthritis, or excessive alcohol intake.




The decision to intervene with pharmacologic therapy involves clinical judgment based on a global assessment, rather than BMD measurement alone. All currently approved therapeutic agents for the prevention and treatment of osteoporosis work by inhibiting or decreasing bone resorption.

Bone densitometry can assist in the decision-making process if the patient’s age confers risk, there are no manifestations of disease, and if the decision point is prevention rather than treatment. BMD measurements can also assist in therapy when there are relative contraindications to a specific agent, and demonstrating efficacy could encourage continuation of therapy.

The decision to intervene with pharmacologic therapy involves clinical judgment based on a global assessment, rather than BMD measurement alone. All currently approved therapeutic agents for the prevention and treatment of osteoporosis work by inhibiting or decreasing bone resorption.

Is Calcium Supplementation Associated with Higher Cardiovascular Risk?

Jamaluddin Moloo, MD, MPH Reviewing Margolis KL and Manson JE., Ann Intern Med 2016 Oct 25;

A new guideline suggests that dietary and supplemental calcium intakes lower than 2500 mg daily don't affect CV risk.

Sponsoring Organizations: National Osteoporosis Foundation; American Society for Preventive Cardiology

Target Audience: Primary care providers


Previous meta-analyses of randomized trials suggested an association between calcium supplementation and excess risk for myocardial infarction and stroke (NEJM JW Gen Med Oct 1 2010 and BMJ 2010; 341:c3691; NEJM JW Gen Med Jun 1 2011 and BMJ 2011; 342:d2040). However, this finding has not been observed consistently. To reconcile these conflicting findings, researchers conducted an updated systematic review and meta-analysis of evidence on effects of calcium intake from diet and supplements, alone or with vitamin D, on risk for cardiovascular (CV) disease in generally healthy adults. Four randomized trials and 27 observational studies were analyzed; supplemented daily calcium intake levels ranged from 400 mg to 1600 mg.

Key Points

  • Moderate-quality evidence shows that calcium intake (with or without vitamin D) from food or supplements has no relation (helpful or harmful) with risk for adverse CV events in generally healthy adults.

  • Calcium from food or supplements that does not exceed the tolerable upper level of intake (2000–2500 mg daily) is safe (with regard to CV health).

  • These conclusions about CV safety were based primarily on analysis of observational studies. The authors and editorialists provide reasons to support their view that two previously published meta-analyses, showing excess CV risks in randomized trials, were unreliable; among other things, those randomized trials were not designed primarily to examine CV outcomes.

  • Dietary sources of calcium are preferred over supplemental calcium.


The Institute of Medicine recommends that adults consume 1000 mg to 1200 mg of calcium daily; this new analysis should reassure patients that calcium supplementation to achieve this level is unlikely to confer excess risk for adverse CV events. Given that daily median dietary calcium intake in the U.S. is approximately 700 mg to 1000 mg, most adults shouldn't require more than 500 mg of supplemental calcium daily. However, a lack of excess CV risk should not invite return to widespread calcium supplementation, because data showing that calcium supplements improve bone density or prevent fractures are limited (NEJM JW Gen Med Nov 15 2015 and BMJ 2015; 351:h4580; NEJM JW Gen Med Nov 15 2015 and BMJ 2015; 351:h4183). In addition, excessive calcium supplementation might be associated with risk for kidney stones, cause gastrointestinal side effects, and interfere with absorption of other medications.

Editor Disclosures at Time of Publication

Disclosures for Jamaluddin Moloo, MD, MPH at time of publication

Grant / Research support

Colorado Health Foundation


  1. Chung M et al. Calcium intake and cardiovascular disease risk: An updated systematic review and meta-analysis. Ann Intern Med 2016 Oct 25; [e-pub]. (http://dx.doi.org/10.7326/M16-1165)
  2. Kopecky SL et al. Lack of evidence linking calcium with or without vitamin D supplementation to cardiovascular disease in generally healthy adults: A clinical guideline from the National Osteoporosis Foundation and American Society for Preventive Cardiology. Ann Intern Med 2016 Oct25; [e-pub]. (http://dx.doi.org/10.7326/M16-1743)
  3. Margolis KL and Manson JE.Calcium supplements and cardiovascular disease risk: What do clinicians and patients need to know? Ann Intern Med 2016 Oct 25; [e-pub]. (http://dx.doi.org/10.7326/M16-2193)



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The USPSTF recommends screening for osteoporosis in:

Next Question
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The correct answer is C. You answered E.

The correct answer is "C." The USPSTF currently recommends bone densitometry screening for all women aged 65 years and older. The National Osteoporosis Foundation recommends bone densitometry for postmenopausal females with one or more of the following risk factors: family history of osteoporosis, personal history of low trauma fracture, current smoking or low body weight (<127 lb). Additional risk factors for osteoporosis include female sex, Caucasian or Asian races, alcohol abuse, sedentary lifestyle, and poor intake or absorption of calcium and vitamin D. Smoking is associated with osteoporosis. Diabetes, once thought to protect against osteoporosis, may actually increase the risk of falls and fractures in older adults. The preferred method for measuring bone density is dual energy x-ray absorptiometry (DEXA). All postmenopausal women should consume 1,200 mg of elemental calcium per day in divided doses. The optimal amount of vitamin D is 400 to 800 IU/day. Weight-bearing exercises also strengthen bone. Bisphosphonates are indicated for treatment of osteoporosis and should not be used without a diagnosis. See question 21.2.3.


The physiologic mechanisms affected by medical strategies for the management of osteoporosis include:

The answer is C.

Medical strategies for the management of osteoporosis include bisphosphonate-mediated apoptosis of osteoclasts, suppression of osteoclast activity by calcitonin, increased osteoblast differentiation by selective estrogen receptor modulators, and enhanced vitamin D–mediated intestinal Ca2+ absorption (not secretion).


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