#62

I used to work as a medical statistician before medical school … the incidence of the disease is critically important, a high incidence serious disease with an intervention that only makes a 10% rate reduction has a markedly bigger impact on all cause mortality than a low incidence less serious disease with an intervention that has a much bigger rate reduction. NNT is pretty important in any decision made to decide to treat. We also need to look at what outcome we are avoiding in the NNT and how this balances with the number of people needing to take the drug who don’t end up with benefit, but end up with risk/cost/side effects.
The extent of costs, side effects, alternatives must be factored before looking at whether Rx.
Naturally picking patients at high incidence of the given adverse outcome is important, and one’s ability to correctly pick those patients so that we treat patients at highest risk (which unfortunately we don’t do that great of a job predicting who will get spinal or hip fractures).
Irrespective, the decision to prescribe lipid medication is a more simple one than this - and I have very few patients who would meet any criteria to consider giving these medications.

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#63

Come on, this is just nit-picking. Neither the results of the RCT or the OS trials were statistically significant, per the diagrams you just noted. His statement “taking these drugs has not been convincingly shown to prevent fracturing your hip in the first place” remains true, per the data presented.

Wait, now you’re expecting him to selectively dismiss the RR for the summation of the RCT+OS studies and just present the RR for the RCTs alone because that suits your pro-pharmacy narrative marginally better? And HE is the one who is biased?

“The RCTs were strictly designed, conducted, and
reported, and the OSs employed multivariate statistical
analysis to minimize potential confounding. The quality of
all included studies was regarded as high.”

Is your strategy here to just get so far into the weeds that nobody will actually get in there to check your work? Actually reading through the review paper (which took some doing to find the full text), re-listening to Dr. Greger’s video, and taking into account Dr. Fraser’s comments above, I think Greger has it right.

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#64

Because a RCT is a better study design and doesn’t have confounding to a similar extent, so it is better able to detect causality.

Greger is wrong and knowingly so on so many topics, so it’s likely he is wrong on this one too.

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#65

Sure, but there’s also the “totality of evidence”. Even if RCTs (if done well) are weighted more heavily than observational trials, it doesn’t mean one has to completely throw out the results of well-done observational trials, especially when both showed significant results in secondary prevention of hip fractures.

We’ll have to agree to disagree, then. Nobody’s perfect, but I think he’s right on the vast, vast majority of topics. And the statement “knowingly” implies that you have psychic powers.

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#66

I love that you are on the board! You challenge me to think and evaluate what I do and recommend. Your points are well made. I’ll continue to refine my approach.

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#67

Novel formulations of oral bisphosphonates in the treatment of osteoporosis

“The cardiovascular effects of bisphosphonates are debated, with data from animal studies (using higher dosages than used in human studies) suggesting potential cardiovascular protective effects due to reduced atherosclerosis in response to bisphosphonate therapy [27–30]. This is supported by a limited signal from a trial of risedronate which showed a protective effect of 2.5 mg dose for cardiovascular mortality (RR 0.69, 95% CI 0.49–0.99) and stroke mortality (RR 0.36, 95% CI 0.17–0.78), though this effect is caveated by the fact that there was no significant effect at the 5 mg dose or on the incidence of coronary artery disease [31]. Indeed, meta-analyses have shown no significant associations (either protective or adverse) between bisphosphonates and cardiovascular death, adverse cardiovascular outcomes, myocardial infarction or stroke [32] and this is echoed by long term, prospective database studies [33].”

“Oral bisphosphonates play a key role in the treatment of osteoporosis and the amelioration of fracture risk. They are, however, hampered by adverse events, particularly affecting the upper gastro-intestinal tract, which reduce patient adherence and persistence. Effervescent alendronate and gastro-resistant risedronate seek to improve adherence by simplifying the complex dosing rigmarole and reducing upper gastro-intestinal adverse events. Data from trials and real-world data are encouraging with regard to the benefits of these medications both clinically and from a health economic perspective.”

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#68

Bisphosphonate drug holiday: who, when and how long

“The four nitrogen-containing bisphosphonates currently in clinical use for the treatment of osteoporosis differ in the strength for binding to bone. The rank order for binding affinity is zoledronate > alendronate > ibandronate > risedronate [Russell et al. 2008]. Higher-affinity bisphosphonates will bind avidly to the bone surface but will spread through bone more slowly, while lower-affinity agents will be distributed more widely through the bone but have a shorter residence time in bone if treatment is stopped. These agents also differ in the potency for inhibiting farnesyl pyrophosphate synthase. The rank order of potency for inhibiting this enzyme is zoledronate > risedronate >> ibandronate > alendronate [Russell et al. 2008]. Bisphosphonate use results in a rapid and substantial decrease in bone turnover markers that is dose and compound dependent, with a maximum effect in 3–6 months. This effect is maintained in a new steady state for at least 10 years with continued treatment [Bone *et al.*2004].“

“In conclusion, bisphosphonates that have been approved for the treatment of postmenopausal osteoporosis are effective and generally safe agents that have robust evidence for fracture risk reduction. Their systemic safety is related to their binding to bone and lack of uptake by other tissues other than the kidney. A reservoir of bisphosphonates accumulates after years of treatment that is gradually released over months or years and appears to result in a lingering antifracture benefit for some time after therapy is stopped.“

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#69

[!]Chinese paper[!].

Non-nitrogen-containing bisphosphonates and nitrogen-containing bisphosphonates for the treatment of atherosclerosis and vascular calcification: A meta-analysis

“The role of non-nitrogen-containing bisphosphonates (non-N-BPs) and nitrogen-containing bisphosphonates (N-BPs) in the treatment of atherosclerosis (AS) and vascular calcification (VC) is uncertain. This meta-analysis was conducted to evaluate the efficacy of non-N-BPs and N-BPs in the treatment of AS and VC.”

“Non-N-BPs and N-BPs did not affect serum calcium, phosphorus or PTH levels. Non-N-BPs decreased serum TC levels and increased serum TG levels. N-BPs did not affect serum lipid levels. Non-N-BPs had a beneficial effect on VC, and N-BPs had a beneficial effect on AS.”

Cardiovascular Safety and Effectiveness of Bisphosphonates: From Intervention Trials to Real-Life Data

“Osteoporotic FF are known to increase mortality, thereby reducing the risk of new clinical fractures by means of antiosteoporosis drugs could also lead to a lowering in number of deaths. Currently, it is unclear whether this effect is a consequence of abatement of new fractures’ number or a direct result of pharmacological intervention with BSPs.”

“Despite these real-life results, a recent meta-analysis by Cummings and colleagues, including 27 clinical trials and 56,737 participants, concluded that no significant association subsists between BSPs and overall mortality, suggesting that BSPs cannot be recommended to increase life-span but only to reduce fracture risk [41].

In conclusion, even if some previous studies have reported that BSPs are associated with reduced mortality in addition to reduced fracture risk, currently there are no sufficient data to recommend the treatment for this reason alone, regardless of the personal risk of fracture. Conversely, it can be stated that mortality rates are no higher in BSP users, reassuring healthcare providers on their use in clinical practice to reduce fracture risk.“

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#70

Rats.

Omega-3 attenuates the severity of medication-related osteonecrosis of the jaws in rats treated with zoledronate

Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite

“Adherence in the presence of pamidronate was higher than with other bisphosphonates. Density Functional Theory analysis showed that the protonated amine group of pamidronate, which are not present in clodronate or zoledronate, forms two additional hydrogen bonds with hydroxyapatite. Moreover, the reactive cationic amino group of pamidronate may attract bacteria by direct electrostatic interaction.”

“Conclusion: Increased bacterial adhesion and biofilm formation can promote osteomyelitis, cause failure of dental implants or bisphosphonate-coated joint prostheses, and complicate bone surgery in patients on bisphosphonates.”

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#71

Short-term bisphosphonate treatment reduces serum 25(OH) vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers

“This study demonstrated that serum 25(OH)D3 became significantly decreased after only 4 months of BP treatment in Japanese osteoporotic patients and confirmed that MIN more strongly inhibited bone turnover as compared with RIS.”

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#72

Pilose Antler Extract and Hydroxytyrosol combination supplement:

”In a parallel randomized, double-blind, placebo-controlled clinical trial, postmenopausal women who received Ruiling capsules for 32 weeks showed marked improvements in lumbar-spine and femoral-neck BMD, bone turnover markers, antioxidant enzyme activities, and reduced low back pain compared to the placebo group. No adverse effects were observed…”

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#73

Healthy bone remodeling is catalyzed by weight bearing activity. One way to get an effect similar to weight bearing walking or running is to stand on a vertical linear platform (it must be vertical, not linear). I would not do this instead of walking and other weight bearing, but the platform is a nice addition. I use it for ten minutes four or five times per week as part of my exercise routine.

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#74

DXA scores may exaggerate the results for slim, thin-boned individuals making them look worse than they are. And, as you said it’s bone quantity vs bone quality.

#75

The DEXA Scan is listed as Gold Standard, but from my research may not be the best and may exaggerate the scores of slim, thin-boned people due to the formula which divides bone mass by square centimeters of the area tested. I believe an accurate formula would be density = mass/volume. So, I present a variety of alternative tests. I will be scheduling the REMS to double-check my DXA scores. And, I will be pursuing diet, supplements and physical exercises to improve my osteoporosis. None of the medications look good to me – well, maybe hormone therapy of some type?

Bone Density Testing Methods Comparison Table

Test Name Method Sites Measured Accuracy (vs. fracture risk) Radiation Cost (Est. USD) Notes / Strengths
DXA (DEXA) X-ray dual-energy absorptiometry Spine, Hip, Femur, Forearm ★★★★☆ Low $100–$300 Gold standard; high reproducibility; widely available
QCT (Quantitative CT) CT scan + software-based BMD analysis Spine, Hip ★★★★★ (Volumetric) Moderate $300–$500+ Measures trabecular bone; more sensitive to changes; higher radiation
pQCT (Peripheral QCT) CT at extremities Forearm, Tibia ★★★☆☆ Low $150–$350 Evaluates bone geometry, strength; not for central sites
REMS (Radiofrequency Echographic Multi Spectrometry) Ultrasound + AI signal processing Spine, Femur (not hip directly) ★★★★☆ None $150–$300 Radiation-free; better for small-boned or osteopenic individuals; not yet widespread
QUS (Quantitative Ultrasound) Ultrasound through heel (calcaneus) Heel only (not central sites) ★★☆☆☆ None $40–$100 Low cost, portable; screening only; not diagnostic of spine/hip BMD
BMAD (Bone Mineral Apparent Density) Calculation using DXA values Spine, Hip (adjusted for size) ★★★★☆ Same as DXA N/A Useful in small-framed people; improves accuracy of DXA
TBS (Trabecular Bone Score) Textural analysis of DXA spine scan Spine only ★★★★☆ None $40–$100 extra Adds quality/density info to DXA; improves fracture risk prediction

:star:

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#76

stand on a vertical linear platform

Deborah, I don’t understand what you mean? Can you provide more details?

#77

Perhaps of interest:

Peter Attia explains that not all DEXA scans are equal and highlights what to look for in a quality scan.

Here are the key points from the video “Not All DEXA Scans Are Equal—Here’s What to Look For” by Peter Attia:

  • DEXA Scan Basics: DEXA (Dual-Energy X-ray Absorptiometry) uses low-dose X-rays to assess fat, lean mass, and bone density. It’s a quick, low-radiation procedure that differentiates between bone, fat, and lean tissue. ​⁠
  • Not All DEXA Scans Are Equal: Many DEXA providers only report total body bone mineral density (BMD). For meaningful insights, it’s essential to get a scan that provides segmental analysis—specifically for the left hip, right hip, and lumbar spine. ​⁠
  • What to Ask For: Before booking, confirm the provider offers segmental bone analysis and full segmental lean tissue analysis. This allows calculation of indices like appendicular lean mass index, fat-free mass index, and fat mass index. ​⁠
  • Cost Differences: Basic scans (body composition only) are cheaper (around $100–$150), while full segmental analysis can cost up to $400, depending on location. ​⁠
  • Interpreting Results: DEXA results are best understood using Z-scores and T-scores, which show how your bone density compares to a reference population (Z-score: age-matched; T-score: young healthy adults). These scores are more clinically meaningful than raw BMD numbers. ​⁠
  • Understanding the Bell Curve: Z-scores indicate where you fall on a normal distribution. For example, a Z-score of 0 means you’re at the 50th percentile; +1 is above 82.5% of the population; +2 is above 97.5%. ​⁠
  • Age, Gender, and Race Matter: Bone density varies by age, sex, and race. Women experience a sharp drop in BMD at menopause. Non-Hispanic Black individuals tend to have higher BMD than non-Hispanic Whites, who in turn have higher BMD than Mexican-Americans. ​⁠
  • When to Get a DEXA Scan: Standard guidelines recommend women start at age 65 and men at 70, with earlier screening for high-risk individuals. The World Health Organization suggests screening women by age 40. Attia personally supports earlier screening, especially for women in their 30s. ​⁠
  • Clinical Relevance: Attia emphasizes that low Z-scores in younger adults are concerning and should be addressed early, just like other metabolic risk factors. ​⁠
  • Final Advice: Always ensure your DEXA scan provides detailed, segmental data for both bone and lean tissue to get the most actionable health insights. ​⁠
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#78

Incase this is helpful, I thought I’d share that my doctor agrees with you and he doesn’t want me on the osteoporosis medicines.

If the TBS test is on your radar, I thought I’d share I recently did this at Simon One, and the entire test, including Dexa, was cash pay $250. That was less than my out of pocket pay for my ‘covered’ regular dexa.

My bone quality was good, whew!! If it was poor, then I might have considered more drastic measures, including the medications.

PS, I might have the smallest bones of anyone you’ve ever met, so the REMS test sound interesting. From your chart, it appears it’s for people who do not have advanced osteoporosis (I have it in 2 out of 3 places). Google tells me it might be better at detecting small changes when trying to do more frequent monitoring of changes. I’d love to hear about anything you’ve learned on this topic. My thought now is to monitor once per year just to make sure I’m moving in the right direction.

#79

Beth,

Tell me more about the TBS and Simon One if there is any more.

I don’t know if my osteoporosis is considered advanced or not. I’ll check and if it is I’ll research the REMS in more detail to make sure it will be useful in case “my case” is advanced.

I’ve come across “The Dr Doug Show” on YouTube. He has a lot of videos on a lot of bone density topics. I find the information he is providing is more along my line of thinking even though I do realize that he is a good salesman and that he does profit from services he provides. However, I believe he does provide clear, honest research information that I can’t find from my doctor.

Here are his basic 4 approaches:

1. Remove

  • Identify and eliminate causes of bone loss, such as nutrient deficiencies (e.g. vitamin D or K2), medications (e.g. steroids), chronic inflammation, or unhealthy lifestyle habits.

2. Replace

  • Restore essential nutrients that support bone remodeling—especially calcium, vitamin D₃, vitamin K₂ (MK‑7), magnesium, and trace minerals—ideally through high-quality supplementation or nutrient-rich whole foods.

3. Rebuild

  • Stimulate osteogenesis via targeted weight-bearing resistance and impact exercise routines. The Dr Doug Show emphasizes heavy resistance training and high-impact exercises to promote bone formation over mere maintenance.

4. Restore Hormones & Metabolism

  • Address underlying hormonal imbalances (e.g. thyroid, estrogen, testosterone, cortisol) and metabolic disruptions that interfere with bone health and bone-building capacity—often done through personalized medical optimization.
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#80

I’ll look up Dr Doug, thx

I don’t have anything interesting to share re the Simon Med TBS dexa (I mistakenly referred to them as Simon One, which s their clinic that offers whole body MRI), but here is a link DEXA + TBS (Trabecular Bone Score) | SimonMed

A few months ago they sent me an email announcing they started offering it, so I went. They did tell me the technology is a few years old, but it was just new to them, so you could check to see if others offer it near you. They only offer TBS at a handful of their clinics. I had to drive 2 hours!

I started hrt a couple of years ago and I take that along with a lot of K and D. In the fall, after a bad dexa, I started taking calcium. I had been concerned due to having a high CAC score, but I was assured there was nothing to worry about.

I also take Taurine which I hear might help (Agetron swears by it!)

I started LDN in Jan, and since then, someone posted an interesting result about someone on rapa and LDN.

My recall of this is a little fuzzy, so grain of salt, but I think it was after the PEARL trial, that a woman on rapa and LDN discovered she grew, maybe, 15% of bone back in a short amount of time. I was hoping lighting would strike twice and that was my incentive to go test again after only 6 months.

In those 6 or 7 monts, My spine was a tiny bit better, my femoral neck was the slightest bit worse (maybe .1), and my hip improved and is no longer osteoperosis

My result could be the natural variation between machines, or from more resistance training, or the calcium, or the LDN… .there is no way to be sure.

If my bone quality was poor or if the numbers moved in the wrong direction, I might have then had a more serious talk with my doc about the various medications

Edit:
I found an article about the woman in the PEARL trial I mentioned

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