Bone densitometry is not a good predictor of hip fractureForAgainst

Dear Sir: Debate For and Against Bone Densometry

Your Debate is timeous (6 October 2001;323:795-799). Serial measurement of RELATIVE bone density (by whatever method) surely does measure bone turnover (and relative stability and risk). But prognostication is more practical, affordable and multifactorial with combined serial measurement [-of bone sonar; sex hormone balance; and balance of fat and lean mass by bio-impedance analysis BIA]- than just bone. BIA and sex hormones allow relative quantification and thus regulation of fat mass for obesity/ immune risks, lean mass for muscle mass ie activity.

Prevention of disease should be directed at multi-system protection, not
just at one system eg cardiovascular, mood, brain, bone, skin, muscles, immunity or urogenital. Only balanced micronutrient replacement (with mineral, vitamin and systemic human sex-hormone replacement SHR) achieves all this simultaneously, safely, successfully and affordably - at perhaps £50 yearly for both sexes. Synthetic wannabe (hormone) substitutes eg SERMs, SARMs, SSRIs, Viagras, phosphonates & statins at ten times the cost, do not. As your Debate says, the major risk factors for fractures are falls and multiple system failure, not isolated bone density. Hence the chief need is improving motor function, balance and control in all systems – which the listed micronutrients do, but not synthetic antiresorptives.

Reproduction aside, hundreds of studies on Medline the past decades have shown the optimal normative prime sexhormone levels (in nmol/L) that are associated with robust youthful health – E2 estradiol 0.1-0.15 in men, about 0.2-0.3 in women; testosterone 30-40 in men, 1.5-2.5 in women; hence the optimal youthful testosterone:E2 ratio (given normal SHBG and other estrogenics) is about >270:1 in men, 3-7:1 in women. But after the third decade, the major anabolic hormones (androgens, calciferols and to a degree progestins) generally decline steadily, but the fattening if not catabolic hormones (non-estradiol estrogenics, cortisone, insulin, prolactin and sexhormone binding globulin) are not allowed to, if anything they rise.

Hence while mood, memory, bone and (skeletal and cardiac) muscle mass generally fall with aging, body fat(and hence apathy, withdrawal, diabetes, arthritis, vasculopathy and cancer) generally increase; so that it has become abundantly clear that optimal prime human sex hormone balance is associated with decades’ more health; and that even with disease (including cancer if monitored and treated) balanced hormone replacement is beneficial.

Suppliers and new drug promoters do not broadcast the reality known for 50 years, that: due to hepatic first pass and non-linear absorption, neither oral sex hormones nor biannual implants are physiological replacement; that “normative” oral estrogen - Premarin - is abandoned by 85% of women by three years; that costly implants and hormone patches cause intolerance/ rejection in 8-15% of women; that in women as in men, testosterone is also needed to balance estradiol; that oral sex hormones have to be taken at 10-20 times higher dose to achieve the same target bloodlevels; while with conventional implant (or depot injection) regimes, the target optimal physiological hormone bloodlevels are attained for only a fraction of the time – the adverse pendulum effect shown well by Nieschlag and Behre(1990, 1998).

But using long-available proven depot sexhormone injections, we have found for years that appropriate weekly subcutaneous self-injection into the upper outer gluteal fat gives optimal physiological levels and symptom control due to painless injection and slower smoother absorption.

Hence from “middle age” – or earlier in case of chronic symptoms- for optimal multisystem health on average Western intake (and how few manage to optimize diet and lifestyle)?), simple supplements do best: dolomite about 1.8g/day (which usually includes 600u Vit D); vitamin C 0.5g/day; fluoride 0.5mg/day; a good multivitamin; with measurement of appropriate non-stressed fasting early morning blood levels eg testosterone, estradiol, sex hormone binding globulin, gonadotropins thyroxine; hemoglobin; prostate-specific antigen, cholesterol, calcium, magnesium, glycosylated hemoglobin, and urea as risk markers, along with usual physical examination including bone ultrasound and measurement of height, mass and body fat and lean mass.

In men, if plasma testosterone is repeatedly much below 2(-30)nmol /L, trial of depotestosterone (enanthate or cypionate) 50 then 100mg sc/week should be prescribed for at least a few months’ trial, then permanently.

For postmenopausal women, a combined weekly sc injection similarly need cost very little: estradiol valerate (eg Primogyn Depot, -Schering-10mg/ml) 0.4(-1.0)mg/week if the blood E2 is much below 0.12nmol/L (in the presence of normal SHBG), plus depotestosterone 5(-10)mg/week if the testosterone level is below about 1.5nmolL(and of course unopposed estrogen-progesterone therapy will suppress the testosterone level and balance); plus if appropriate, depot progesterone (MPA) at 3 times the E2 dose ie 1.5-3(0.01-0.02ml) mg/week.

The fixed combinations Mixogen(Upjohn) and Primodian Depot (Schering) (testosterone esters 93-100mg, estradiol esters 4-5mg/ml) have worked superbly well for decades at about 1ml every 4-6 weeks – but (like the now-condemned Sustanon) with unphysiological highs and lows; so for convenience we titrate 0.1(-0.2) ml/week. It is obvious that since humans convert testosterone to E2, less E2 need be given in the combination than using E2 alone.

Using testosterone and estradiol esters enables physiological plasma sexhormone levels to be monitored occasionally- which is not possible with eg Premarin, Decadurabolin, Estinyl, estrone or estriol as the replacement agents.

We have discussed physiological subcutaneous sex hormone repeatedly with many gynecologists, andrologists and internists worldwide; all agree with the logic, although such an economic, safe the promoters and effective regime is anathema to of new patent substitutes.
The reality is that, vaccination aside, since the early 1960s, no new synthetic drug has been proven to significantly reduce all-cause mortality, increase survival, as prevention of the common major preventable degenerative diseases of aging, since metformin and betablockers, let alone the earlier vitamins, human hormones, aspirin, digitalis, and the older synthetics. Only adding vigorous physiological testosterone replacement (plus estrogen in women) reverses terminal wasting and depression in AIDS patients on antiretrovirals(Rabkins; Grinspoon et al 1998+)
No gynaecologist is able to explain rationally why- despite all major hormone replacement now using physiological human hormones (eg insulin, thyroxine, testosterone, growth hormone, erythropoeitin) – only postmenopausal women are ordered to take grossly unphysiological xenohormones (Premarin orally)- which (apart from nausea in up to 20%) give them foreign (equilin) bloodlevels manifold higher than the needed E2 levels.
The answer lies in commerce: funders (Drug and Equipment developers) understandably refuse to fund trials comparing patent drugs (eg Premarin, statins, biphosphonates, SERMs, Viagra, SSRIs) with systemic low-cost human sex hormone, vitamin and mineral replacement, since they know that their patent drugs will be discredited. This is despite published proof that the incidence of breast cancer rises increasingly after more than 15 years of Premarin use (Henderson et al 1995), and that Premarin doubles the normal postmenopausal fat gain to about 2.7kg/year while doubling the leanmass loss to about 2kg/year(Aloia et al 1995) – giving a “trivial” net weigh gain of Hence only Premarin/Prempak equivalents (not systemic safe lowcost physiological estradiol plus testosterone) are apparently being funded(eg by Wyeth/Ayerst, and Solvay) as the HRT in current major USA and European trials; and only costly DEXA BMD, biphosphonates and raloxifene are promoted for osteoporosis trials….

yours,

Dr Neil D Burman
Preventative Internist,

Cape Town, RSA ndburman@bigfoot.com

Refs & further reading:

1. Nieschlag E & Behre HM eds: Testosterone Action Defieiency Substitution: Springer, Berlin, 1990, 1998.

2. Bhasin S et al: The Therapeutic Role of Androgens: Bailliere’s Clinical Endoc metabolism 1998:12 number 3:365-542.

3. Studd JWW ed et al: The Millennium Menopause Review: London 2000.

4. Weiss M, Ben-Shlomo A, Hagag P et al: Novel Quantitative Ultrasound at the Radius and multi-sites: Osteoporosis Int: 2000:11:411-6 & 688-696.