Forteo. July 30, 2001 Eli Lilly and Company announced that the Food and Drug Administration (FDA) received the unanimous recommendation of the Endocrinologic and Metabolic Drugs Advisory Committee to approve Forteo as a treatment for osteoporosis in postmenopausal women. The committee was split 5-5 on recommending it for men. The FDA generally follows the recommendations of the advisory committee, but they are not bound to follow them.
Forteo has been involved in 25 clinical trials enrolling more than 2,800 men and postmenopausal women with osteoporosis. Important Phase III clinical trial data published May 10, 2001 in The New England Journal of Medicine showed that the investigational drug stimulated new bone formation, significantly lowered fracture risk and significantly increased bone mineral density compared with placebo in participants with osteoporosis during an average of 18 months of treatment.
Although men were not recommended for approval, and assuming the FDA doesn`t ultimately approve Forteo for men, they will surely be able to use the medication as an off-label drug just as they did with Fosamax when it was first approved. One can only guess as to why men weren`t included in the recommendation, and I don`t want to guess. I will tell you that men with idiopathic osteoporosis have been found to respond to parathyroid hormone-(1,34) (PTH) with marked increases in both spinal and femoral neck bone mineral density (BMD). See J. Clin Endocrinol Metab 2000 Sep;85(9):30069-76, Kurland ES and others, Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. PMID: 10999788. In this study ten patients received 400 IU PTH and 13 patients received vehicle only by daily subcutaneous injection during the 18-month study. When comparing the results, those men in the treatment group had a 13.5% increase in BMD at the lumbar spine and 2.9% increase in femoral neck BMD relative to controls. The authors concluded: "PTH is a potent stimulator of skeletal dynamics in men with idiopathic, low turnover osteoporosis; is associated with substantial increases in lumbar spine and hip bone density; and may prove to be an efficacious anabolic agent in men with this disorder." (See the Ask the Expert segment for more information about Forteo).
Heart attack diagnosis. I very rarely cover issues not directly related to osteoporosis, but think this study is pertinent to all of us and is potentially live saving in nature, so I will mention it. I have a friend who recently had a heart attack or myocardial infarction (MI). He was seen in the emergency room of a good hospital where initial testing that was done did not discover his problem. He lay in a hospital bed all night in pain with what was ultimately 60% loss of his cardiac function due to the failure to diagnose his MI. Had his physician followed the recommendation in the study I`m about to cite, they would have known within 90 minutes with 100% certainty that my friend had an MI, thus allowing rapid, proper treatment to begin. See the IntelliHealth Professional Network Web site at http://ipn.intelihealth.com/IPN/ihtIPN?st=23883&t=7223&c=334047 for a summary of the article. This Web site is a good one to allow you to keep up with medical developments as they will send a free email with timely medical updates. See the study in Am J Cardiol 2001;88:611-17, by Ng, SM and others, Ninety-minute accelerated critical pathway for chest pain evaluation. PMID: 11564382. The authors studied 1,285 consecutive patients with chest pain who attended a hospital emergency room. They used (along with normal EKG or other testing) three diagnostic laboratory tests: cardiac troponin I (cTn1), myoglobin, and creatine kinase-MB (CK-MB). These three tests detected 100% of patients who had an MI, and just as importantly, 100 percent of those who hadn`t had one. This reduced cardiac care unit admission by 40%, with 90% of patients with negative tests allowed to go home and only one returning in 30 days with an MI (0.2%). All testing was accomplished within 90 minutes. If any or all markers are positive, this confirms that an MI occurred. If all are negative, this rules out an MI. I have printed out the IntelliHealth summary and placed it in my wallet. Should I or a friend develop chest pain, I want to be able to assure myself that proper procedures are followed to adequately diagnose or rule out an MI. Note that negative testing doesn`t rule out cardiovascular changes that could later lead to an MI. It only tells you that no heart muscle has been damaged yet. Thus, additional testing, such as, tread mill stress testing, Ultrafast CT(R) scan (see http://www.maleosteoporosis.org/special.htm for my experience with this), nuclear scans, etc., may be needed. Ask your physician about these.
Ask the expert
More on Forteo. Since Forteo is presumably about to be approved by the FDA as a treatment for osteoporosis, I asked Dr. Karen Kolba, our expert advisor in osteoporosis to the Men`s Osteoporosis Support Group, for more information about it.
Questions. Here are some of the questions I have about Forteo.
1. Do you recommend it for men? If so, do you have a particular T-score that you consider the cut-off point where you would prescribe it, if so what?
2. What is the cost of it per day and do you expect any problems getting HMOs to pay for it?
3. Do you anticipate men taking it only for a relatively short period, e.g., one year, then maintaining gained bone via bisphosphonates? If not that regimen, which would you suggest?
4. Are there any side effects or complications from it that concern you if men take it?
5. Should it be taken in conjunction with bisphosphonates or only taken alone? If they aren`t taken in conjunction, I assume there would be no problem just stopping the bisphosphonate for someone currently taking that drug, and then starting Forteo.
Answers. It is impossible to answer many of these questions yet as I can`t even get answers from Eli Lilly, the manufacturer of Forteo. Even THEY may not know right now as they are in negotiations with the FDA about the recommendations on how to use the drug, and they won`t say anything about the price. We should know a lot more in three months.
For your information, I wouldn`t have a problem prescribing it for men, and it is not clear that the labeling is going to exclude men anyhow. The T-score below which it will be indicated is part of those "negotiations." I do know it will be used for one year as daily subcutaneous injections with possible extension for a second year-but not beyond that. It would not make sense to take anti-resorption drugs (bisphosphonates) along with the one that promotes bone growth. But, after PTH therapy is done, I would think everyone would go back on a bisphosphonate.
Literature review
Finding articles mentioned. To see abstracts of these articles, go to PubMed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi and enter the numeric portion only of the PMID into the search block and click on Go or hit the enter key.
Glucocorticoid-induced osteoporosis. The American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis published their latest recommendations for prevention and treatment of glucocorticoid-induced osteoporosis in Arthritis Rheum 2001 July 2001(7):1496-503. PMID: 11465699. The paper points out that glucocorticoid therapy is associated with multiple side effects, one of which is bone loss with resultant increased fracture risk. Many studies have shown that patients treated with glucocorticoid therapy often do not receive treatment to prevent bone loss. Thus, these new guidelines are published to update physicians as to the latest research since the 1996 recommendations.
"The committee recommends obtaining a baseline measurement of bone mineral density (BMD) at the lumbar spine and/or hip when initiating long-term (i.e., >6 months) glucocorticoid therapy." They note that Medicare will reimburse for bone density testing for patients receiving long-term glucocorticoid therapy at doses >7.5 mg/day.
Studies have shown that patients starting long-term glucocorticoid therapy with normal BMD levels can often maintain starting bone levels if placed on 1,000 mg/day of calcium and 500 IU of vitamin D or an active vitamin D metabolite. Calcium supplements alone have not been shown to be effective . The authors note, "Therefore, supplementation with both calcium and vitamin D should be required for glucocorticoid-treated patients."
Glucocorticoid therapy may cause hypogonadism due to inhibition of secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary gland. Thus, both males and females receiving long-term glucocorticoid therapy should be assessed for hypogonadism. If tests reveal low levels of hormones, then appropriate hormone replacement therapy (HRT) should be instituted. In women, HRT has been shown to retain and increase BMD while they are on long-term glucocorticoids. In men, testosterone replacement has been shown to increase spine BMD, but not hip BMD. The committee suggests, ". . .men with serum testosterone levels below the physiologic range (<300 ng/ml) should receive replacement therapy." They suggest this should only begin after proper prostate cancer diagnostic testing as prostate cancer is an absolute contraindication to testosterone replacement therapy.
Five large clinical trials have shown that bisphosphonates (etidronate, alendronate, and risedronate) are effective in both the prevention and treatment of glucocorticoid-induced osteoporosis. Improvement occurs regardless of age, sex, and menopausal status in women. The paper concludes that, "Glucocorticoid-treated premenopausal women, postmenopausal women receiving HRT, and men should be treated with either alendronate 5 mg/day or risedronate 5 mg/day." They also state, "Calcitonin is not recommended for prevention of bone loss in patients beginning glucocorticoid treatment. The same holds for fluoride.
Summary of committee recommendations. All patients beginning long-term glucocorticoid therapy should modify lifestyle risk factors such as smoking and excessive alcohol consumption. They should begin a weight-bearing exercise program, take calcium and vitamin D supplements. Then patients are broken into two categories with the following additional suggestions:
1. Patients beginning therapy with a prednisone equivalent of >5 mg/day for > 3 months. These patients should receive bisphosphonates (use with caution in premenopausal women.)
a. Prescribe treatment to replace gonadal sex hormones if deficient or otherwise clinically indicated.
b. Have BMD measured at the spine and/or hip. If low (T-score below -1):
1) Prescribe bisphosphonate (use in caution with premenopausal women).
2) Consider calcitonin as a second-line agent if patient has contraindication to or does not tolerate bisphosphonate therapy.
c. If BMD is normal, follow up and repeat BMD measurement either annually or biannually.
Editor`s comments on committee recommendations.
1. The committee recommends bisphosphonates as a preventative measure at the start of long-term glucocorticoid therapy. Yet they only recommend it if BMD T-score is below -1 for patients currently receiving long-term therapy. This is rather puzzling to me and I don`t understand their reasoning. If they want to prevent lost BMD in one instance, why not in the other since bisphosphonates have been shown in multiple studies to prevent glucocorticoid-induced bone loss?
2. A baseline BMD measurement seems appropriate in all cases of glucocorticoid therapy, and appears to be the committee`s recommendation in the body of the report, so I wonder why they did not suggest that for patients beginning therapy in the summary section. Comparison with standards for BMD is one thing, but comparison with your own starting BMD is certainly more accurate and revealing of the effects of glucocorticoid therapy. Thus, I think these rather equivocal recommendations leave patients as the losers and unnecessarily complicate physicians` recommendations to patients.
3. The paper rather strongly suggests that vitamin D and calcium supplements are adequate therapy to prevent bone loss while patients with normal BMD receive long-term bisphosphonates. Yet, all five of the large clinical trials of bisphosphonates they cite used calcium and/or calcium plus vitamin D supplements with both test and control subjects. All five studies found that BMD decreased or remained level in the placebo group (receiving only calcium and/or calcium and vitamin D) while it increased in the test groups receiving bisphosphonates and supplements. Clearly this indicates the superiority of bisphosphonates compared to calcium and vitamin D for maintenance and increase in BMD while patients receive long-term glucocorticoid therapy. Note that in one study in Calcif Tissue Int 2000 Oct;67(4):277-85 by Wallach S and others, Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy, PMID: 11000340, patients on 5 mg/day of risedronate had a 70% reduction in fracture risk compared to controls receiving calcium and vitamin D supplements. I don`t want to increase my fracture risk by 70% to save some money by taking only cheaper calcium and vitamin D supplements, do you?
4. In summary, I would like to see the committee restate their recommendations with the unequivocal recommendations for pretreatment BMD measurement and bisphosphonate therapy for all patients beginning or currently receiving long-term glucocorticoid therapy. This gives patients maximum protection from unnecessary bone loss or fracture, and simplifies physician guidelines tremendously, thus assuring better compliance with committee recommendations.
People at risk for osteoporosis
Antiepileptics. Several recent studies suggest risk factors for osteoporosis that are not commonly mentioned in osteoporosis literature on or Web sites. The first two articles concern antiepileptic drugs. The first suggests that valproate therapy puts patients at increased risk for osteoporosis. It is by Sato Y and others and is published in Neurology 2001 Aug 14;57(3):445-449, Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy, PMID: 11502911. The authors used BMD of the second metacarpal on 40 epileptic adults taking valproic acid (VPA), 40 taking phenytoin (PHT), and compared that to 40 age-matched healthy control subjects. With VPA they found BMD reduced 12% in men and 16% in women; with PHT the reduction was 12% in men and 15% in women. Nine patients taking VPA had T-scores below -2.5 SD suggesting osteoporosis while 15 patients had T-scores between -1 and -2.5 SD suggesting osteopenia. Measurement of bone markers suggests excessive bone resorption is the cause of bone loss. The authors conclude, "Long-term VPA monotherapy can increase bone resorption, leading to decreased BMD." The next paper explains that antiepileptic drugs (AEDs) have been shown to be associated with bone disorders since the late 1960s. The severity of bone and biochemical abnormalities is thought to correlate with the duration of AED exposure and the number of AEDs used. The AEDs most commonly associated with altered bone metabolism are phenytoin, primidone and phenobarbital. New anticonvulsants such as lamotrigine, topiramate, vigabatrin, and gabapentin have not been associated with bone metabolism problems. See CNS Drugs 2001;15(8):633-42, Pack AM and Morrell MJ. Adverse effects of antiepileptic drugs on bone structure: epidemiology, mechanisms and therapeutic implications. PMID: 11524035. Readers should be aware that they might be at risk for osteoporosis if they are taking antiepileptic medications. One member of the group takes Valproate for headaches, and it is used for depression, bipolar disorder, etc. So it is not only epilepsy that could put you at risk. When you start new medications, check the Internet or pharmacology texts to find any and all side effects from those medications.
Chronic lung diseases. For information on the relationship between chronic lung diseases and osteoporosis see Rev Mal Respir 2001 Sep;18(4):411-15, Brousse C and others. Bone mineral density in patients with chronic lung diseases. PMID: 11547249. The authors studied a group of 43 men and 15 women with a mean age of 44 years who had chronic obstructive diseases (25 patients), cystic fibrosis (19 patients), and other lung diseases (14 patients). They concluded, "Chronic lung disease can lead to osteoporosis. Corticosteroids, low vitamin D level, sedentary lifestyle, smoking, and in cystic fibrosis nutritional deficiencies, delayed puberty and hypogonadism are risk factors. Bone density must be measured in order to prevent and treat osteoporosis."
Testosterone treatment for hypogonadal men. There are a couple of interesting articles on this subject in the recent literature. The first is in Endocr Pract 2000 Mar-Apr;6(2):132-8, by Guay AT and others, Testosterone treatment in hypogonadal men: prostate-specific antigen level and risk of prostate cancer. PMID: 11421528. This study looked at pre- and post-testosterone replacement therapy PSA levels of hypogonadal men. Ninety consecutive men with erectile dysfunction received either testosterone enanthate IM injections, 200 or 300 mg every 2 or 3 weeks (N=25); testosterone non scrotal patches, 5 mg daily (N=16); or clomiphene citrate, 50 mg orally three times weekly, in patients with functional secondary hypogonadism (N=49). After 2-3 months of treatment, PSA levels were reassessed, and those with suspicious digital rectal examine (DRE) or increased PSA levels underwent prostate biopsy. The authors found that PSA levels increased in both age groups: those aged 40 to 60 and those aged 61 to 80 years old. The clomiphene group had the greatest increase in PSA, the nonscrotal patch group had the least, and the testosterone injection group was intermediate. Ten men underwent prostate biopsy, nine for elevated PSA levels and one for a nodule found on DRE. A total of three men had prostate adenocarcinoma upon biopsy for a total yield of 3.3%. The authors point out that testosterone levels and prostate cancer risk are a debatable issue with some studies indicating a possible link between elevated testosterone levels and prostate cancer and others studies not finding that link. One goal of this study was to find the expected increase in PSA that should develop after men are placed upon testosterone therapy. They found for nonscrotal patches in younger patients it was 0.20 ng/ml, and for older patients it was 0.23 ng/ml; for testosterone injections in younger patients it was 0.32 ng/ml and for older patients it was 0.94 ng/ml; for clomiphene citrate it was 0.8 ng/ml in younger patients and 1.2 ng/ml for older patients. The authors suggest that all men about to undergo testosterone therapy should have PSA levels tested and a DRE. Additionally they state, "Because the PSA levels are inappropriately low in patients with hypogonadism, caution is warranted if the PSA level is high-normal before testosterone therapy is begun. In addition, a post-treatment PSA level that increases more than the normal range for age should raise suspicion about prostate disease. We suggest that follow-up PSA levels should be obtained 6 months after testosterone treatment is begun and then yearly thereafter." They conclude, "We agree with others that, in light of an increasing PSA level or a change in the findings on DRE (or both), ultrasonographic guided biopsy of the prostate should be performed."
This study is interesting as it gives some expected norms to measure and compare increased PSA levels after patients begin testosterone therapy. Without understanding that the PSA levels can increase as a result of beginning testosterone therapy, both the patient and physician might interpret the increases incorrectly. This could lead to unnecessary fear or biopsy. But, this study doesn`t seem to implicate the commencement of testosterone therapy with an increased risk for prostate cancer. That brings us to the next article, a letter to the editor in the same journal. See Endocr Pract 2000 Mar-Apr;6(2):218-21 by Morley JE, Testosterone treatment in older men: effects on the prostate. PMID: 11421536.
To explain what this article is about, here is a quote from the second paragraph, "Standard medical `mythology` is that prostate growth is accelerated by testosterone. That belief has persisted despite the fact that benign prostatic hyperplasia (BPH) is a disease of older men." He also states, "Similarly, nearly 75% of prostate cancers are diagnosed in men older than 65 years of age. Thus, we have to face the conundrum that prostate disease occurs at a time when testosterone levels are declining dramatically!" In older individuals, testosterone therapy has been shown to have a multitude of benefits: increased muscle mass and strength, increased bone mineral density, improved libido, decreased age-related cognitive dysfunction, decreased leptin levels, decreased ST-segment depression in persons with coronary artery disease. But, would giving them testosterone supplements increase their risk for prostate cancer? There are many studies that indicate no added risk, including the Guay`s study above. He cites other placebo-controlled trials that show either no change or a small increase in PSA levels associated with testosterone treatment. In a review article of 16 studies of testosterone therapy in men older than 40 years of age, in 13 studies no increase in PSA level was noted. Thus, if PSA is an index of prostate activity, testosterone has little effect on the prostate. In three retrospective studies, there was no increase in BPH or prostate cancer with testosterone therapy. Additionally, a study of transdermal dihydrotestosterone treatment in 37 older men for 6 months to 5 years did not show increased PSA levels, and the prostate size (measured by ultrasonography) was significantly reduced by 15.4%. Conversely there are implications that testosterone does cause prostate cancer. This includes Finasteride, a drug used to treat BPH that blocks a pathway in testosterone production, and also reduces prostate volume by 24-27% and decreases PSA levels by about 50% in some studies. Also, in a Veterans Affairs cooperative study in 1967, castration resulted in symptomatic relief, but no extension of life, for men with prostate cancer. Another study found 45 of 52 men with prostate cancer had unfavorable responses when treated with testosterone. However, all these men had metastatic disease when therapy started. Thus, this is a complex issue and the next decade of research should provide answers to the safety and efficacy of male HRT. The author concludes, "On the basis of available data, testosterone treatment in older men with androgen deficiency seems unlikely to have major effects on prostate growth. Nevertheless, testosterone treatment should clearly not be used in patients with known prostate cancer. When testosterone treatment is initiated in older men, PSA levels should be monitored at regular intervals."
What I get as a bottom line from these two studies is that fear of testosterone therapy is probably over stated as a cause of prostate cancer or BPH. The important thing is to follow-up early after the institution of therapy with PSA level testing and DRE in the event an early prostate tumor was undetected and that testosterone therapy would stimulate tumor growth. After that period, a man on testosterone therapy should be tested for PSA levels and have DRE on regular intervals just as a man not on therapy should be tested.
Testosterone Gel. I covered the use of testosterone (T) gel as an alternative testosterone replacement therapy in the April 2001 newsletter: http://www.maleosteoporosis.org/18nl.htm. There is a recent study with additional information on the use of gel in Clin Endocrinol 2001 Jun;54(6):739-750, by Wang C and others. Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men. PMID: 11422108. This is the six-month results from a multi-center clinical trial involving 227 hypogonadal men, mean age 51 years. Participants received either 1% T gel with either 50 or 100 mg T (delivering 5-10 mg T/day), or two T patches (delivering 5 mg T/day). At day 91 T gel dose adjustment up or down occurred to deliver 75 mg/day for three additional months. Results showed that 100 mg/day of T gel resulted in serum T concentrations 1.4 and 1.9 fold higher than T gel 50 mg/day and the T patch groups, respectively. Proportional increases occurred in serum oestradiol. BMD increased significantly both in the hip (+1.1 +/- 0./3%) and spine (+2.2 +/- 0.5%) only in the T gel 100 mg/day group (P=0.0001). The authors conclude, "Transdermal testosterone gel applications for 6 months decreased bone resorption makers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. Ongoing long-term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone administered." As pointed out in the April 2001 newsletter, T gel is considerably more expensive, but considerably more convenient and painless that other methods of testosterone replacement therapy. It will be easier to justify the expense of its use if long-term studies confirm the efficacy noted in this study.
Dairy intake and osteoporosis. In the October 2000 newsletter http://www.maleosteoporosis.org/16nl.htm there was a thorough discussion of the issues involving calcium intake from dairy foods and its relationship to osteoporosis. A recent Italian study reveals some additional information about this issue. See Osteoporos Int 2001;12(4):296-301, Varenna M and others. Unbalanced diet to lower serum cholesterol level is a risk factor for postmenopausal osteoporosis and distal forearm fracture. This study assessed whether dietary changes aimed at reducing serum cholesterol can increase the risk of osteoporosis (OP) and fracture. It involved 311 postmenopausal women with high serum cholesterol levels who were on a diet low in dairy products with calcium intake less than 300 mg/day for about 27 months. These women were compared to 622 healthy postmenopausal women paired for age and age at menopause, and with calcium intake estimated at more than 1 g/day. The authors found the prevalence of OP was significantly higher in women with low dairy calcium intake (42.1% vs. 22.3%; p<0.0001), as was the number of Colles` (distal wrist) fractures (4.5% vs. 1.6%; p=0.008). The authors conclude, "Dietary intervention methods to lower serum cholesterol in postmenopausal women should maintain an adequate calcium intake by providing calcium from low-fat dairy products or calcium supplements." So, efforts to treat one condition should not overlook the possible effects on other organs, systems, etc. This is strong evidence that drastic reduction in calcium intake has serious negative effects on BMD and fracture rate. There is no reason to assume it applies only to postmenopausal women, so men should consider its results applicable to them, too.
Kyphoplasty and vertebroplasty. When acute spinal compression fractures are present, kyphoplasty (KP) and vertebroplasty (VP) are two options that could provide pain relief. Especially in the case of kyphoplasty, functional improvement as well as decreased kyphosis are also possible. There is a segment devoted to this topic on the Men`s Osteoporosis Support Group Website at http://www.maleosteoporosis.org/pv.htm if you want additional details. Also, see the recent review article in Spine 2001 Jul 15;26(14):1511-1515 by Garfin SR and others. New technologies in spine: kyphoplasty and vertebroplasty for the treatment of painful osteoporotic compression fractures. PMID: 11462078. I will briefly summarize some important points from this article.
VP involves the injection of a plastic material into the vertebral body which hardens to stabilize it thus decreasing pain. KP uses an inflated balloon within the vertebra to elevate it and to create space for the plastic material that is injected in a softened form, and that ultimately hardens and stabilizes the vertebra. All of this is done in the operating room using fluoroscopy and/or other X-ray techniques and is followed by a 1-3 day hospital stay. Studies using VP have reported 70-90% success in relieving pain, but most are small studies with limited follow up. KP has been used only since 1998. One ongoing multicenter study of 376 procedures on 340 patients has early results. Significant improvement in increased vertebral body height has been noted, often gaining back to the range of 90% of pre-fracture height. Significant complications reported for VP are less than 10% and include, increased pain, radiculopathies, spinal cord compression, pulmonary embolism, infection, rib fractures. Cement leakage is common, but not necessarily serious unless it endangers the spinal cord, blood vessels, or other vital tissues. For KP, there are four important complications caused by the devices (0.7% per fracture and 1.2% per patient). These include, one patient with transient fever and hypoxia; one patient with an epidural hematoma when heparin was administered 8-hours postoperatively; one patient with partial motor loss to the lower extremities, and one patient developed anterior cord syndrome. Complications have been related to the needle insertion, not the balloon. In summary, KP appears to be the method of choice, preferably as soon as possible after spinal compression fracture occurs, and ideally no later than three months thereafter. Treatment should be at a major medical center using a highly experienced medical team. Neither technique is risk-free, but the vast majority of cases report improvement, and often significant and rapid improvement.
Disclaimer. Diagnosis and treatment of osteoporosis are the responsibility of the patient and his or her physician. Nothing in this newsletter is to be interpreted as a recommendation for treatment or to change treatment that your physician has prescribed. Although we attempt to assure that information in this newsletter is factual, errors will occur. It is the responsibility of the reader to verify that information they are acting on is factual. There is no relationship between this newsletter and any national osteoporosis group, including the National Osteoporosis Foundation. All references to any such groups are for informational purposes only.
