Does it protect bone?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01SermorelinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 139 people given it.8 reported

   19 people given it1 trial1 found nothing

   • found nothingThe hormone response faded while the injections carried on. Nineteen adults aged 55 to 71 injected salt water nightly for a month, then a sermorelin-like peptide for four more months. Growth hormone and its main blood marker rose within two weeks, stayed up for three months, then drifted back to where they started even though dosing never stopped. Muscle, insulin response, mood and libido improved in the men and not the women. Bone density and sleep did not change in anyone.

     The numbers 19 adults aged 55 to 71 on 4 weeks of placebo then 16 weeks of the Nle27 analogue at 10 micrograms/kg nightly: IGF-1 and IGFBP-3 rose within 2 weeks and returned toward baseline by week 16 while dosing continued. Lean mass, insulin sensitivity, well-being and libido improved in men only; bone mineral density and sleep quality did not change.

     Journal of Clinical Endocrinology and Metabolism, 1997· 19 people

2. 02Thymalin with epitalonBlendStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,106 people given it.7 reported

   0 people given it1 trial

   • This is the study the thymalin story rests on, and it is not built to carry that weight. 266 older people were followed for six to eight years, and given thymalin and epithalamin in the first two or three. Infections and deaths were reported at about half the rate of a comparison group, and several age-related diseases as less common. The problem is this. The paper does not say anyone was grouped by chance or kept unaware of their treatment. And no other team has repeated it.

     The numbers 266 elderly and older persons assessed over six to eight years, with thymalin and epithalamin applied during the first two to three years. Acute respiratory disease incidence fell 2.0 to 2.4-fold, with reduced clinical ischaemic heart disease, hypertension, deforming osteoarthrosis and osteoporosis against control. Mortality fell 2.0 to 2.1-fold with thymalin, 1.6 to 1.8-fold with epithalamin and 2.5-fold with both, and a separate group treated with both annually for six years had a 4.1-fold lower mortality rate. Single group, no described blinding or randomisation, never replicated.

     Neuro Endocrinology Letters, 2003· number of people not given

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01ResveratrolSupplementModerate. At least one finished study in people, and at least 100 people who took it. 14 completed trials, 403 people given it.7 reported

   0 people given it1 trial

   • The same trial found a real gain in bone. After a year on 75 mg twice daily, bone density in the lower spine rose against the dummy, the hip score improved a little, and a marker of bone being broken down fell. Estimated ten year fracture risk came down. Women with the worst bone markers gained most, as did those also taking vitamin D and calcium. What was measured was density and blood markers. Nobody counted a single broken bone.

     The numbers The bone arm of RESHAW. After 12 months on 75 mg twice daily, lumbar spine bone density rose 0.016 g/cm2 versus placebo, femoral neck T-score improved 0.070, C-terminal telopeptide (a resorption marker) fell, and FRAX ten-year major and hip fracture probability dropped. The benefit was larger in women with poor bone biomarker status and in those also taking vitamin D plus calcium. Density and markers, not fractures.

     Journal of Bone and Mineral Research, 2020· number of people not given

2. 02Vitamin K2SupplementPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.1 reported

   nobody was given it1 watch-only study

   • Healthy women past menopause who took a low dose of K2 for three years lost less bone. That is bone density, not broken bones, and it was not a test of living longer.

     The numbers Randomised MK-7 for three years in healthy postmenopausal women. Reported attenuated bone loss. Not a fracture-outcome trial and not a general-population longevity trial.

     Osteoporosis International, 2013· number of people not givenobserved only, nobody was given it

Approved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.

1. 01Zoledronic acidSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 4 completed trials, 7,176 people given it.

   5,065 people given it3 trials

   • The bone drip prevented broken bones in older women with thinning bones. Two thousand New Zealand women aged 65 and over got four infusions of either the drug or plain salt water over six years, spaced eighteen months apart. Fragility fractures happened in 122 women on the drug and 190 on salt water. Roughly fifteen women had to be treated for one to avoid a fracture. The trial was built to count fractures, not deaths, so it cannot tell you whether anyone lived longer.

     The numbers 2,000 New Zealand women aged 65 or older with osteopenia, randomised to four infusions of 5 mg zoledronate or saline at 18-month intervals over six years. Fragility fracture occurred in 190 on placebo and 122 on zoledronate, hazard ratio 0.63 (95 percent CI 0.50 to 0.79). Number needed to treat 15. This is the large trial in older women, and its primary endpoint was fracture, not mortality.

     New England Journal of Medicine, 2018· 2,000 people

   • Fewer heart attacks, cancers and deaths turned up on the bone drip, but this was a side look, not the question the trial asked. It re-counted the illnesses and harms recorded in the same two thousand women. Heart attacks fell from 39 women to 24. Cancers fell by about a third. Deaths leaned lower without being clearly separable from chance. The authors say these hints justify a trial built from the start to measure them, which is a polite way of saying this one cannot settle it.

     The numbers Adverse event analysis of that same 2,000-woman trial. Myocardial infarction in 39 women on placebo against 24 on zoledronate (hazard ratio 0.60, 95 percent CI 0.36 to 1.00). Total cancers reduced, hazard ratio 0.67 (0.51 to 0.89). Hazard ratio for death 0.65 (0.40 to 1.06, p equals 0.08), and 0.51 (0.30 to 0.87) in women without an incident fragility fracture. The authors state these apparent effects justify further appropriately powered trials with these nonskeletal conditions as primary endpoints.

     Journal of Bone and Mineral Research, 2020· 2,000 people

   • A once a year bone drip after a broken hip cut later fractures, and fewer people died. Around two thousand people, average age in their mid seventies, got the drip or a dummy one within three months of hip surgery, then were followed about two years. New fractures hit about 9 in every hundred on the drug and about 14 on the dummy. Deaths fell too, roughly a quarter fewer. Death was not what the trial was built to measure. Fever and aching muscles were the usual side effects.

     The numbers HORIZON Recurrent Fracture Trial, NCT00046254. 1,065 assigned to yearly 5 mg intravenous zoledronic acid and 1,062 to placebo within 90 days of hip fracture repair, mean age 74.5, median follow-up 1.9 years. Primary endpoint new clinical fracture: 8.6 percent against 13.9 percent, a 35 percent reduction. In the safety analysis 101 of 1,054 (9.6 percent) on drug and 141 of 1,057 (13.3 percent) on placebo died, a 28 percent reduction in all-cause death, p equals 0.01. Mortality was not the primary endpoint. Commonest adverse events were pyrexia, myalgia and bone and musculoskeletal pain; no osteonecrosis of the jaw was reported.

     New England Journal of Medicine, 2007· 1,065 people

2. 02PioglitazoneSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 9,114 people given it.5 reported

   3,876 people given it1 trial

   • In people with insulin resistance but no diabetes who had just had a stroke or a mini-stroke, pioglitazone lowered the chance of another stroke or a heart attack over about five years. It also halved new diabetes. It cost more weight gain, swelling and broken bones. Death rates were about the same.

     The numbers 3,876 patients without diabetes, with insulin resistance and a recent ischaemic stroke or TIA, randomised to pioglitazone (target 45 mg daily) or placebo, median 4.8 years (IRIS). Stroke or myocardial infarction in 9.0% versus 11.8% (HR 0.76, 95% CI 0.62 to 0.93, p=0.007). Diabetes in 3.8% versus 7.7% (HR 0.48). All-cause mortality similar (HR 0.93). Weight gain over 4.5 kg 52.2% versus 33.7%, oedema 35.6% versus 24.9%, fracture needing surgery or hospitalisation 5.1% versus 3.2%.

     The New England Journal of Medicine, 2016· 3,876 people

3. 03DHEAHormoneModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 267 people given it.5 reported

   243 people given it2 trials1 found nothing

   • found nothingThe biggest study of DHEA against a dummy pill as an anti-ageing supplement found nothing that mattered. 144 older men and women with low levels took it for two years. The hormone went up and little else changed. Body shape, strength, fitness, blood sugar control and quality of life did not get better. Bone density went up slightly at one spot in men and one in women. These were healthy volunteers with low levels, not patients.

     The numbers 144 people, 87 men and 57 women aged 60 or over with low DHEA-S, randomised double-blind to 2 years of oral DHEA, testosterone (men only) or placebo. DHEA raised serum DHEA-S by a median 3.4 mcg/mL in men and 3.8 in women. No significant effect on body composition, peak oxygen uptake, muscle strength, insulin sensitivity or quality of life. Small gains in bone density at the femoral neck in men and the ultradistal radius in women. No major adverse effects.

     The New England Journal of Medicine, 2006· 144 people

   • Frail older women given DHEA along with gentle exercise got a little stronger in the legs. Bone density did not change over six months. Small and short. Everyone exercised, so this compares DHEA plus exercise against exercise alone.

     The numbers 99 frail women, mean age 76.6, with low DHEA-S and low bone mass, randomised double-blind to 50 mg DHEA daily or placebo for 6 months, all on calcium, vitamin D and twice-weekly exercise; 87 completed. Bone mineral density and bone turnover markers were flat. Lower extremity strength rose from 459 to 484 N (p=0.01) and Short Physical Performance Battery score from 10.1 to 10.7 (p=0.02) on DHEA.

     Journal of the American Geriatrics Society, 2010· 99 people

4. 04MK-677Small moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 65 people given it.11 reported

   nobody was given it1 watch-only study

   • The trial was stopped early over a heart safety signal, and most of what it measured did not improve. 123 older people recovering from a broken hip took MK-677 or a dummy pill. Walking speed improved and IGF-1 rose. Most other measures of function did not move. The study was halted before it finished because of concern about congestive heart failure in treated patients. Stopping early leaves the benefit thin and the harm not properly measured.

     The numbers 123 elderly hip-fracture patients: gait speed improved and IGF-1 rose, but most functional measures did not, and the trial was terminated early over a congestive heart failure safety signal.

     Archives of Gerontology and Geriatrics, 2011· number of people not givenobserved only, nobody was given it

5. 05OxandroloneHormonePreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.5 reported

   nobody was given it1 watch-only study

   • Oxandrolone left badly burned children with stronger bones five years later. 119 children with burns over 30 percent of their body got the drug twice a day for up to two years, or a dummy pill. Treated children had stronger bones across the whole body and lower spine, and grew taller faster early on. Fewer had bones weak enough to raise fracture risk. Two years of treatment beat one. No harm was blamed on the long course.

     The numbers Randomised, up to 24 months of oxandrolone in severely burned children with five-year follow-up. Significant improvement in whole-body bone mineral content, lumbar spine bone mineral content and density, and height velocity, with treated children showing significantly greater height velocity throughout the first two years post-burn. Fewer treated children had bone density z-scores below minus 2.0, indicating reduced future fracture risk. Two years of treatment produced significantly greater gains than twelve months. No adverse effects were attributed to long-term administration in this cohort.

     Shock, 2016· number of people not givenobserved only, nobody was given it