WEEK 8: Golden Guidelines

Lena T -

Hello everyone! Happy Warm Weather~

As promised last week, I will be going into guidelines that are in place in different areas. I found an article called Osteoporosis: A Review of Treatment Options and it goes quite in-depth into different treatments compared the one I covered last week.

In this article, they made a really interesting conclusion. They concluded that there is an expected increase in medical visits, hospitalizations, and nursing home placements due to osteoporotic fractures and will contribute to an economic burden on the healthcare systems.  How can we avoid this expected increase? According to the article, they stated that although BMD screening and treatment with medication is important, Osteoporosis (OP) is preventable with proper management of diet and lifestyle.


  • peak bone mass is highly dependable upon genetics but many modifiable factors can influence bone mass such as nutrition, exercise, and certain diseases/medications


  • published screening for OP guidelines vary greatly
  • benefit of screening for early detection is proved by Barr et al. trial after randomly selecting 4,800 women from 45-54 years old and 25.9% decreased in fracture risk
  • Gold standard for diagnosing
    • Dexa scan and looking especially at the hip and lumbar
    • T-scores interpreting BMD
  • Lack of consistent evidence on how frequent a patient should get a DEXA scan
    • National Osteoporosis Foundation recommends 1-2 years after initiation of treatment and every 2 years afterward
    • Gourlay et al. and Berry et al. suggests to get a DEXA scan every 4 years
    • North American Menopause Society states that repeated testing in untreated post-menopause patients is not recommended until  2-5 years has passed and stated that it is not useful to get constant DEXA scan until 2 years into treatment
  • Recent progression towards OP detection
    • A new diagnostic instrument: FRAX by University of Sheffield
    • FRAX takes account of age, race, alcohol, gender, BMI, smoking, parental history, use of glucocorticoids, and DEXA scan to estimate appropriate patient treatment
    • It has limitations:
      • Does not account for those already receiving treatment
      • Does not account for ages outside 40-80 years old
      • Does not account for fall history

Guidelines (these are the popular ones that the article picked out)

  • AACE/ACE (Postmenopausal Osteoporosis)
    • with no prior fractures or at moderate risk
      • Alendronate, Risedronate, Zoledronic acid, or Denosumab (Prolia, Amgen) are the first line options
      • Ibandronate and Raloxifene are alternatives
    • with prior fractures or at high risk
      • Denosumab, Teriparatide (Forteo, Lilly) and Zoledronic Acid are first line options
      • Alendronate and Risedronate are alternatives
    • High risk is defined by old age, fragility, use of glucocorticoids, and low T-scores
    • Raloxifene or Ibandronate may be used initially for spine-specific therapy
    • Sequential Therapy of Teriparatide followed by an Anti-Resorptive medication is supported
    • Combinational Therapy for treatment is not recommended due to limited availability of data, increased cost, and potential side effects


  • NAMS 2010 (Postmenopausal Osteoporosis)
    • Postmenopausal women need to implement dietary and lifestyle changes to reduce modifiable risk factors
    • Bisphosphonates are usually recommended at first line options but Raloxifene should be considered for younger menopausal patients or with low BMD to prevent bone loss and reduce vertebral fractures
    • Calcitonin is not recommended at first line options and it is considered for women five years beyond menopausal


  • Endocrine Society 2012 (Men)
    • Generic
      • Alendronate (preferred)
    • Recent hip fractures
      • Zoledronic acid
    • High risk males
      • Teriparatide (increases BMD in spine more than Alendronate)
      • Risedronate as an alternative
    • They recommend nonoral therapy for those with gastrointestinal problems


  • ACR 2017 (Glucocorticoid Induced Osteoporosis)
    • patients starting long-term glucocorticoid therapy fracture risk must be re-evaluated every 12 months
    • Postmenopausal women, men 40+, and adults 30+ using 30 mg+ of glucocorticoid treatment
      • Bisphosphonate  (preferred over Teriparatide, Denosumab, or Raloxifene)


  • NOF 2014 (Postmenopausal women and men 50yo)
    • expresses guidance on diagnosis and screening
    • no recommendation for treatments or one superior over the other


  • American College of Physicians 2017 (women and men)
    • Women
      • Alendronate, Risedronate, Zoledronic Acid, or Denosumab for 5 years is appropriate
    • Men
      • Bisphosphonates
      • Author’s data on men are sparse
    • For women 65 yo with Osteoporosis
      • recommend treatment needs to be individualized
    • They are against treatment with menopausal estrogen therapy treatment with estrogen or progestogen



  • Nonpharmacological Management
    • adequate calcium and Vitamin D intake
    • weight-bearing exercises
    • smoking cessation
    • limitation of alcohol/ caffeine consumption
    • Institute of Medicine (IOM)
      • recommend dietary calcium intake limited to 1000 mg daily for men 50yo-70y0
      • 1200mg for women 51+ and men 71+
      • published literature on calcium and risk of developing kidney stones, it is important to differentiate effects of dietary calcium and supplemental calcium from vitamins, high intake of calcium from supplements may increase the risk of kidney stones, however, high intake of dietary calcium may protect against kidney stones
      • recommends dietary calcium intake be increased first before calcium supplements
    • NOF and American Society of Preventative Cardiology funded their own studies
      • recent debates about calcium intake are linked to cardiovascular events
      • the studies concluded that dietary and supplemental calcium intake that does not exceed upper limit recommended by the IOM poses neither cardiovascular risk or harm nor benefit for generally healthy adults
      • Vitamin D is the key component in caclium absorption and bone health and IOM recommends 600 IU per day for men and women 51-70yo and 800 IU for men and women older than 70yo
      • Recent studies debate that too much Vitamin D can be associated with increases risk of falls….
  • Pharmacological Treatment
    • Goal: reduce risk of fractures
    • Anti-resorptive vs Anabolic
      • Anti-resorptive: decrease rate of bone resorption
      • Anabolic: increase bone formation more than bone resorption
    • Not all drugs are FDA approved
  • Anti-resorptive Agents: Biphosphonates
    • AACE/ACE, ACR. NAMS, and Endocrine Society recommends Bisphosphonates (excluding ibandronate) as first line option for prevention
    • Bisphosphonates: bind with high affinity to mineral matrix of bone and inhibit OCs resorption, leading to decrease bone turnover and net gain in bone mass
    • Bisphosphonates are available in many formulations
      • Oral: Alendronate, Risedronate, Ibandronate  (Alendronate is available as tablets with a combination formulation with Vitamin D)
      • Immediate release/delayed release: Risedronate (delayed is not inferior to immediate)
      • IV Injections: Zoledronic Acid, Ibandronate
    • Bisphosphonates are excreted by kidney, toxicity may occur in renal impaired patients
    • Oral Bisphosphonates have to taken with a full glass of water in the morning on an empty stomach 30 mins before to a meal or any other medications  (60 mins if it is ibandronate) while sitting upright to prevent esophageal irritation
      • adverse reactions: gastrointestinal discomfort, heart burn, indigestion, esophageal erosion, esophageal ulcers
    • All bisphosphonates associated with rare complication of osteonecrosis in the jaw
      • Osteonecrosis in the jaw is observed in patients who have received prolonged bisphosphonates and undergo invasive dental procedures
      • Zoledronic Acid has highest risk for osteonecrosis in the jaw
      • IV injections may cause reactions like fever, muscle aches so it may require pretreatment with oral medication
      • increased risk of atypical femur fractures
    • FDA 2010 released a safety communication that long term use can cause femoral fractures –> recommendation: drug holidays
      • Taking drug holidays when risks outweigh the benefits
      • Moderate risk: drug holiday after 3-5 years of oral medications or after 3 annual IV Zoledronic Acid
      • High risk: drug holidays after 6-10 years of oral medications or 6 annual IV zoledronic acid (pt can take Teriparatide or Raloxifene during holidays)
  • Anti-resorptive Agents: Denosumab
    • FDA approved for Postmenopausal women with high risk
    • AACE/ACE recommends it as a first-line therapy for pts at high risk and cannot take oral therapy
    • Denosumab: first biologic agent available for treatment, fully human monoclonal antibody inhibits RANKL to decrease bone resorption
      • injectable formulation (60mg every 6 months) administered by a healthcare professional
      • adverse effects: hypersensitivity, serious infections, dermatological reactions, muscle pain, hypercholesterolemia, hypocalcemia, osteonecrosis, and atypical femoral fractures
      • sever risk of hypocalemia in patients with severe renal impairment
    • RANKL: transmembrane protein required for formation, function, and survival of osteoclasts
    • it is approved for women with breast cancer receiving adjuvant aromatase inhibitor therapy and men with OP and prostate cancer receiving drug therapy
    • Safe for patients with chronic kidney disease stage 1 to 3 but not stage 5
    • drug holidays are not recommended due to rapid decrease in BMD

Hormonal Therapy 

  • Estrogen Agonist/ Antagonists (aka SERMS –> Selective Estrogen Receptor Modulators)
    • Raloxifene
      • acts as estrogenic agonist on bone by decreasing bone resorption and bone turnover thus BMD increases
      • also estrogen antagonistic activity on breast and uterine tissue (recommended for women with high risk of fractures and developing breast cancer)
      • dosed at 60 mg/day without regard to food
      • adverse events: vaginal bleeding, hot flashes, worsening of pre-existing hypertriglyceridemia, venous thromboembolism, death to stroke, and cardiovascular disease
      • should be avoided if women have a history of cardiovascular issues, pre-menopausal, pregnant, or breastfeeding
    • Conjugated Estrogen/ Bazedoxin (Duavee, Pfizer)
      • FDA approved it in 2013 based on 3 clinical trials that demonstrated reduced hot flashes, used in postmenopausal womenw ith intact uterus for prevention and treatment for vasomotor symptoms
      • reduce risk of endometrial hyperplasia
      • contains 0.45mg of conjugated estrogen and 20mg bazedoxifene –> taken once daily
      • increased BMD in hip and spine but due to lack of fracture data, actual efficacy is unclear
    • Estrogen-Progestin Therapy
      • FDA approved solely for prevention of OP in high risk women when all other treatment is exhausted
      • adverse effects according to Women’s Health Initiative: increased risk of cardiovascular events, stroke, invasive breast cancer
      • the risks exceeds benefits, hormonal replacement therapy is no longer recommended as first-line for treatment and prevention
    • Testosterone Therapy
      • limited studies have been done
      • Endocrine Society recommends antifracture treatment and testosterone together
      • Monotherapy (just Testosterone) is recommended when patient’s testosterone level is less than 200mg/dL or have symptoms of androgen deficiency or hypogonadism
    • Calcitonin
      • synthetic polypeptide hormone with properties similar to natural calcitonin found in mammals, bird, and fish
      • effects on human bone physiology is unclear but calcitonin receptors were found on the surface of OCs and OBs
      • FDA approved for women who have postmenopausal osteoporosis for more than 5 years when all other treatment has been exhausted
      • lacks data showing reduction in nonvertebral fractures (not considered first line options)
      • Calcitonin-salmon nasal spray available as generic, one spray in nostril daily
      • Miacalcin nasal and Fortical is no longer on the market
      • adverse effects: rhinitis, nasal irritation, back pain, arthrolgia, nose bleed, headaches, increases risk of cancer

Parathyroid Hormone Analogue

  • Teriparatide: recombinant human PTH (1-34) analogue
    • mimics physiological actions of PTH in stimulating new bone formation in the surface of the bone by stimulating OBs
    • AACE/ACE suggests use of it for inital high risk postmenopausal treatment with prior fractures and unable to take oral medications
    • it can be taken during biphosphonate drug holidays
    • increases BMD in hip, spine, and total body
    • reported few new vertebral fractures compared to Alendronate but no difference in nonvertebral fractures
    • FDA recommended 20mcg SC once daily in thigh/ abdomen and limited to 2 years due to Osteosarcoma
    • AACE/ACE recommends an antiresorptive agent immediately following teriparatide to avoid bone density decline
    • patient’s should avoid if they have Paget’s disease, bone malignancy, hypercalcemic, hyperparathyroidism
  • Abaloparatide (Tymlos, Radius Health): second recombinant human PTH analogue to reach the market
    • FDA approved it in 2017 and it shows that it reduces new vertebral fracture by 86% over a 18months trial
    • available as an injection, 80mcg SC once daily in abdomen
    • same with Teriparatide, limited to 2 years
    • cheaper than Teriparatide
    • adverse effects: dizzy, nausea, headache, palpitations, fatigue, abdominal pain, vertigo
    • avoid use if patient has hypotension, hypercalcemia, urolithiasis

Emerging newer drugs

  • Romosozumb (Evenity, Amgen): humanized monoclonal antibody inhibits sclerostin
    • sclerotin is a protein secreted by OCs to reduce bone formation by interfering with function of OB
    • FRAME trial (international)
      • had evenity and prolia and data showed 73% lower risk of new fractures in 12months with placebo
      • FDA did not approve it in July 2017 and Amgen is reapplying for application
  • Odanatib: selective CatK
    • 2016, Merek discontinued due to risk of stroke
  • Lasofoxifene (Sermonix): third generation of SERMs
    • PEARL trial: gave 0.25mg and 0.50mg or placebo and 0.5mg patients reduced risk of vertebral fracture by 42% and 24% for nonvertebral fractures and there was also a reduction in breast cancer, coronary heart disease, and stroke
    • it has been approved in Europe but still pending in the US

The article is from February 2018 so some changes could have progressed further, for example, Evenity is now FDA approved. The article did also list a graph of Average Whole Price Ranges for Osteoporosis Medications. Here are a couple of examples:

  • Denosumab (Prolia): every 6 months $1,353.84
  • Zoledronic Acid: Yearly $1,300.60
  • Calcitonin-salmon: $21,921.52

These were my take-ways from the Osteoporosis: A Review of Treatment Options. The article also covers a little bit about cost-effectiveness but it uses a metric system that I can’t quite figure out. It uses $60,000 per quality adjusted life year gained, I would like to continue looking into cost-effectiveness because treatment for Osteoporosis patients isn’t easy and paying for it can be a burden.

I have collected 11 surveys this week by the way! Thank you for checking in! I am excited to be finally making some charts from my data!

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All viewpoints are welcome but profane, threatening, disrespectful, or harassing comments will not be tolerated and are subject to moderation up to, and including, full deletion.

    Toby Chang
    Interesting findings, and I'm glad to hear your surveys are receiving more responses!! You mentioned the economic burden that the repeated visits osteoporosis necessitates - how much of that falls on the healthcare system versus the patient?
    Yajaira Garcia
    This is all very interesting! I like the way you broke down everything.
    Is our system able to lower the rise of visits due to osteoporosis? What have you looked into for preventative measures?
    This is a ton of information, but the way you broke it down made it pretty easy to follow. I am excited to see what the data for your surveys looks like!
    Тerrific work! This is the type of information that should be shared aⅽross the web. Shame on Google for not positioning this put up higher! Come on օver and visit my site . Thanks =)
    Hi Toby! Great Question! With my very little experience with insurance, I believe it varies! Most fractures occur in post-menopausal women, and they have a high chance they qualify for Medicare and usually Medicare is very good about covering 80% of the cost and if the patient has a supplemental that covers the rest of the 20%, it still would be covered by the insurance companies. However, having both Medicare AND a supplemental insurance is very expensive, and many patients cannot afford that. I say that it varies because each state has their own regulations, and each state has their own insurance companies with their own Pros and Cons.
    Hi Sofia! My survey mainly focuses on preventive measures such as organic shampoo vs non-organic shampoo and what kind of food should be part of our everyday diet and how much direct sunlight should we get. I think generally educating the public about Osteoporosis and tips can help lower the amount of visits to the ER.

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