What Patients Need To Know About Osteoporosis

Osteoporosis is a condition that is sure to become increasingly diagnosed as our population ages.
Osteoporosis is significant because it is associated with an increased risk of bone fracture, including fracture of the hip and vertebra, which are the cause of significant morbidity, mortality, loss of independence and medical expense in the elderly. In current clinical practice, osteoporosis is diagnosed on the basis of either the occurrence of a low-impact or fragility fracture, or on the basis of measured low bone mineral density (BMD). A low-impact fracture is one that occurs after a fall from standing height or less; a fragility fracture occurs spontaneously or with no trauma (cough, sneeze, sudden movement).
Bone strength is determined by bone density, bone “quality,” and bone microarchitecture. Of these features, bone density, or mass, is what we are able to measure. Osteoporosis is defined by World Health Organization criteria based on a person’s bone density by dual energy x-ray absorptiometry (DXA). Osteoporosis occurs when bone density is below 2.5 standard deviations from the mean for non-Hispanic white women between ages 20 and 29 (T score < -2.5). Osteopenia is defined by bone density of between 1 and 2.5 standard deviations below the mean for non-Hispanic white women in their twenties (T score of -1 to -2.5).
In recent years a variety of effective medications have been developed and approved for treatment of low bone density. Nonetheless, there are still significant gaps in our knowledge. Recently, the FDA issued a warning about an increased risk of “atypical fractures” that has been observed amongst women who take bisphosphonates, the most commonly prescribed drugs for osteoporosis. A few years ago these drugs were also linked to another rare problem, osteonecrosis of the jaw. This was primarily described in cancer patients and those on cancer medications, but the finding got patients, dentists, and oral surgeons quite worked up over the potential risks.
In clinical practice there is significant variation in the practice of screening for and treating osteoporosis and its precursor, osteopenia. According to national epidemiological data from NHANES III over 56% of women over age 50 have reduced bone density, of these 16% have osteoporosis. In their 80s 87% of women have reduced bone density and 44% of have osteoporosis. The key to prevention and treatment is trying to figure out who and when to treat aggressively to best prevent fractures. Current guidelines by the US Preventive Services Task Force support screening women at age 65. However, many post-menopausal women under age 65 are also at risk and the conservative evidence-based USPSTF guidelines do not comment on which of these women should also be screened. Other professional guidelines, such as those issued by the National Osteoporosis Foundation, support screening younger women who are post-menopausal and who have risk factors.
A variety of clinical tools exist to help women quantify their osteoporosis risk.
Osteoporosis risk factors include:
• Low body weight (<57 kg)


• Asian or Caucasian ethnicity


• Personal history of fragility fracture


• Family history of osteoporosis 


• Smoking


• Drinking > 2 glasses of alcohol per day


• Excessive caffeine intake


• Certain medications (glucocorticoids)


• Sedentary lifestyle


• Amenorrhea (lapses in menstruation prior to menopause)


• Eating disorders


• Marathon running


• Dietary deficiencies of calcium and vitamin D


• Chronic health conditions (chronic liver and kidney disease, rheumatoid arthritis)




Many women fall into these increased risk categories and thus are screened before age 65 leaving them with a diagnosis of osteopenia or osteoporosis and creating the conundrum of what to do for the remainder of a woman’s life.
In general, most women with osteopenia should not receive pharmacologic therapy unless they are higher risk, or have already suffered a fracture. Instead, they should be counseled to institute behavioral measures, such as increased weight-bearing exercise and increases in calcium and vitamin D supplementation. When these women should be rescreened is not clear, but probably no more often than every two years. Tracking the rate of bone density decline may help identify women who subsequently should receive drug therapy.
Effective pharmacologic treatments for osteoporosis are available and are, in general, well tolerated. Medication options include the bisphosphonates: alendronate, residronate, ibandronate and zoledronic acid, hormonal treatments (estrogen and selective estrogen receptor modulators), and recombinant parathyroid hormone (teriparatide). Of these options, the oral bisphosphonates, alendronate (Fosamax) and residronate (Actonel), have the most evidence supporting their efficacy in fracture prevention, and are considered first line. These drugs, however, can be somewhat inconvenient to administer because of their poor bioavailability that requires them to be taken on an empty stomach for best absorption. In addition, they are associated with gastrointestinal side effects—specifically esophagitis, and for this reason are contraindicated in patients with precancerous changes of the espophagus, “Barrett’s Esophagus.” For patients who experience gastrointestinal side effects the intravenous bisphosphonate, zoledronic acid may be administered every one to two years.
Hormonal therapies, such as estrogen, are effective treatment for low bone density. However, as indicated by the results of the Women’s Health Initiate, their use has been associated with an increased risk of breast cancer and cardiovascular disease. Raloxifene, a selective estrogen receptor modulator (SERM), is approved for both prevention and treatment of osteoporosis. Its use, while associated with a reduction in breast cancer risk, is also associated with an increased risk of thomboembolism. Its effect on cardiovascular disease appears to be neutral.
The appropriate duration of therapy and frequency of monitoring patients who are on pharmaceutical treatment are areas that remain ill-defined. Studies have indicated that 5 years of alendronate may be adequate for many average risk women. However, my experience in clinical practice is that many women are left on these drugs for years and years. Some have advocated drug “holidays” after five years of therapy. The largest randomized controlled trial looking at alendronate use and fracture outcomes was 10 years in duration, which in my view calls into question the safety of prolonged use.
Many questions remain about how to approach the treatment of aging bones to prevent the debilitating outcome of bone fracture. Seasoned clinicians have seen the problems that may occur in some cases with treating large populations of well patients for normal life processes (postmenopausal estrogen replacement therapy). Let’s hope that future research will address the question of when to treat with medication and for how long with further precision. Until then let’s use appropriate caution when prescribing medicine for normal senior bones.


by : Juliet K. Mavromatis

Androgen-Deprivation Therapy and Risk for Colorectal Cancer

Androgen-deprivation therapy (ADT) is the standard initial treatment for men with metastatic prostate cancer, yet the majority of men in the U.S. who receive ADT have nonmetastatic disease. Recently, the FDA asked the manufacturers of gonadotropin-releasing hormone (GnRH) agonists to include warnings about the potential risks for diabetes and cardiovascular diseases associated with their products; links between GnRH agonists and fracture risk have also been demonstrated (JW Oncol Hematol Aug 11 2009).

Now, investigators have assessed the potential association between colorectal cancer (CRC) and the use of ADT (with GnRH agonists or orchiectomy). The researchers analyzed Surveillance, Epidemiology, and End Results (SEER) Medicare data for 107,859 men (age, 67) who received initial diagnoses of prostate cancer from 1993 through 2002.

During a mean follow-up of 59.4 months after diagnosis, 2035 patients developed CRC. The incidence of CRC per 1000 person-years was 6.3 for men who underwent orchiectomy, 4.4 for men who received GnRH agonist therapy, and 3.7 for men who received no ADT. The adjusted hazard ratio for orchiectomy versus no ADT was 1.37 (95% confidence interval, 1.14–1.66). CRC risk increased with duration of GnRH agonist use: For 13 to 24 months of GnRH agonist use, the AHR versus no ADT was 1.19 (95% CI, 1.00–1.41), and, for 25 months of GnRH agonist use, the AHR versus no ADT was 1.31 (95% CI, 1.12–1.53).

Editor's Comment: An accompanying editorial notes that obesity is consistently associated with excess risk for CRC in men. Obese men tend to have lower testosterone levels than nonobese men, and both hyperinsulinemia and insulin resistance might be causally linked to obesity and development of CRC. The editorialists also speculate that the increased risk for CRC that was evident so soon after ADT use in the current analysis might reflect the influence of hormones on relatively late processes of carcinogenesis. As the list of risks associated with ADT use increases, the appropriate selection of patients for ADT — as well as the use of aggressive lifestyle and diet modification in those who require ADT— becomes increasingly important.

   Robert Dreicer, MD, MS, FAC

Published in Journal Watch Oncology and HematologyDecember 21, 2010

The Challenge Hypothesis

When Barack Obama won the American presidency in 2008 his supporters cheered, cried, hugged—and in many cases logged onto their computers to look at pornography( :))  ). And, lest Republicans crow about the decadence of their opponents, precisely the obverse happened when their man won in 2004.

That, at least, is the conclusion of a study by Patrick Markey of Villanova University, in Pennsylvania, and his wife Charlotte, who works at Rutgers, in New Jersey. The Markeys were looking for confirmation of a phenomenon called the challenge hypothesis. This suggests that males involved in a competition will experience a rise in testosterone levels if they win, and a fall if they lose.

The challenge hypothesis was first advanced to explain the mating behaviour of monogamous birds. In these species, males’ testosterone levels increase in the spring, to promote aggression against potential rivals. When the time comes for the males to settle down and help tend their young, their testosterone falls, along with their aggressive tendencies.

Something similar has since been found to apply to fish, lizards, ring-tailed lemurs, rhesus monkeys, chimpanzees—and humans. In many of these animals, though, there is a twist. It is not just that testosterone ramps up for breeding and ramps down for nurturing. Rather, its production is sensitive to a male’s success in the breeding competition itself. In men, then, levels of the hormone rise in preparation for a challenge and go up even more if that challenge is successfully completed. Failure, by contrast, causes the level to fall

Previous research has found these hormonal ups and downs in male wrestlers, martial artists, tennis players, chess players and even people playing a coin-flip game. In evolutionary terms, it makes sense. If a losing male continues to be aggressive, the chances are he will be seriously injured (it is unlikely natural selection could have foreseen competitive coin-tossing). Turning down his testosterone level helps ward off that risk. Conversely, the winner can afford to get really dominant, as the threat of retaliation has receded.

For most species, determining that this actually happens requires a lot of boring fieldwork. But the Markeys realised that in the case of people they could cut the tedium by asking what was going on in those parts of the web that provide a lot more traffic than their users will ever admit to, on the assumption that men fired up by testosterone have a greater appetite for pornography than those who are not.

To do this they first used a web service called WordTracker to identify the top ten search terms employed by people seeking pornography (“xvideos” was the politest among them). Then they asked a second service, Google Trends, to analyse how often those words were used in the week before and the week after an American election, broken down by state.

Their results, just published in Evolution and Human Behavior, were the same for all three of the elections they looked at—the 2004 and 2008 presidential contests, and the 2006 mid-terms (in which the Democrats made big gains in both houses of Congress). No matter which side won, searches for porn increased in states that had voted for the winners and decreased in those that had voted for the losers. The difference was not huge; it was a matter of one or two per cent. But it was consistent and statistically significant.

If the polls are right, then, next Tuesday’s mid-term elections will see red faces in the red states for those furtive surfers who are caught in the act. In the blue states, meanwhile, a fit of the blues will mean the screens stay switched off.

6 Fixtures

The schedule til February 19th:

1-Sunday 31 Jan : Gasteroenerology Ward

2-Thuesday 2 Feb : Emergency Ward

3-Thursday 11 Feb : General Medical Ward IV

4-Friday 12 Feb : Rheumatology-Endocrinology Ward

5-Sunday 14 Feb : Emergency Ward

6-Wednesday 17 Feb : General Medical Ward II