Hydroxyapatite for Bone Mineral Density

Oral hydroxyapatite used for bone mineral density means bone-derived products: ossein-hydroxyapatite complex (OHC) and microcrystalline hydroxyapatite compound (MCHC or MCH). In a 60-woman open trial, postmenopausal women who took 3.32 g of OHC a day showed no significant change in bone density over 2 years, while those on 2.5 g of calcium carbonate lost 3.7% in the second year and untreated women lost 3.5% and 5.6% at 12 and 24 months (Castelo-Branco 1999a). A 120-woman open-label trial reported significantly higher osteocalcin with OHC than with calcium carbonate over up to 3 years, with numerically better femoral neck density (no significance test reported), but only 54 completed and the comparator supplied more elemental calcium (1,000 versus 712 mg a day) (Ciria-Recasens 2011).

The double-blind 153-woman trial found OHC and tricalcium phosphate both lowered bone turnover markers but with no significant bone density effect, and a modern 100-woman randomized placebo-controlled trial looked only at markers over 3 months (Albertazzi 2004; Bristow 2014). No trial measured fractures as its main outcome. Guidelines put bisphosphonates first for osteoporosis (ACP 2023; Endocrine Society 2019); see calcium for bone mineral density for the base supplement.

Hydroxyapatite is the mineral of bone, and the NIH notes that more than 99% of the body's calcium is stored as calcium hydroxyapatite in bones and teeth (NIH ODS). Taken by mouth, bone-derived forms are a source of calcium and phosphate. In a 100-woman trial, microcrystalline hydroxyapatite raised ionised calcium less than calcium citrate or carbonate but raised phosphate and the calcium-phosphate product, while lowering bone turnover markers (CTX and PINP) by comparable amounts at 3 months (Bristow 2014).

Lower bone turnover markers show less bone breakdown, not stronger bone. Ossein-hydroxyapatite also contains non-collagen peptides, but the trials cannot separate any effect of those from the calcium and phosphate. In the double-blind trial, 500 mg of calcium as OHC lowered osteocalcin by 12.3% versus 9.9% with tricalcium phosphate, a small edge on markers with no significant density difference (Albertazzi 2004).

Doses in the trials were set by the product, not by any dose-finding study. OHC was given as 3.32 g a day (Castelo-Branco 1999a, 1999b), as two 830 mg tablets twice daily supplying 712 mg elemental calcium (Ciria-Recasens 2011), as 1660 mg every 12 hours in a retrospective cohort (Fernandez-Pareja 2007) and as 500 mg of calcium a day (Albertazzi 2004). MCH supplied 1 g of calcium a day for 3 months (Bristow 2014), and MCHC was given at 6 to 8 g a day for 12 months in people on prednisolone (Pines 1984).

Whatever the product, the calcium counts toward your total: the NIH upper limit is 2,500 mg a day for ages 19 to 50 and 2,000 mg a day from age 51 (NIH ODS).

In 60 postmenopausal women who declined hormone therapy, OHC at 3.32 g a day kept bone density stable across 2 years, while calcium carbonate fell 3.7% (P < .05) in year 2 and the untreated group fell 3.5% (P < .05) and 5.6% (P < .01) at 12 and 24 months; the study was open and allocation was not described (Castelo-Branco 1999a). In 120 women over 65 with osteoporosis, OHC raised osteocalcin more than calcium carbonate (+1.86 versus +0.31 ng/mL at year 3, P < 0.05), with lumbar spine density changes of -1.1% versus -2.3% and femoral neck +2.5% versus +1.2% at 3 years (no significance test reported for density); only 54 of 120 completed, the trial was open-label and the comparator supplied more elemental calcium (1,000 versus 712 mg a day) (Ciria-Recasens 2011).

The double-blind trial randomized 153 osteopenic women with low calcium intake to OHC, tricalcium phosphate or placebo (500 mg calcium a day in each active arm). Both active forms lowered bone formation markers (osteocalcin -12.3% with OHC and -9.9% with tricalcium phosphate at 6 months), but bone density differences did not reach significance; OHC raised spine density by 0.8% at 12 months in the OHC group only (Albertazzi 2004). In 100 women, 3 months of MCH or conventional calcium lowered CTX and PINP comparably, with no density measurement (Bristow 2014).

In 36 patients with chronic active hepatitis on corticosteroids, 2 years of MCHC halted the fall in radius bone mineral content and slowed the fall in iliac crest cortical thickness (P < 0.025), though fractures and back pain differed non-significantly (Stellon 1985). A 40-patient trial found less pain with 6 to 8 g of MCHC a day, but the bone-loss difference from 8 untreated controls came close to, but not to, statistical significance (Pines 1984). Combined with transdermal estradiol, OHC raised bone mineral content 4.7% in one year versus smaller gains with either alone (Castelo-Branco 1999b).

A retrospective 4-year cohort of 112 osteopenic women on OHC reported trabecular T-scores rising from -1.27 to -0.86 (P < 0.0001), with mild constipation in 3.2%, but it had no control group and lifestyle advice was given to all (Fernandez-Pareja 2007).

What's missing: blinded trials with fractures as the outcome, any trial of synthetic nano-hydroxyapatite taken by mouth, trials from groups unconnected to the product, and comparisons with calcium plus vitamin D alone that match elemental calcium.

Bone-derived hydroxyapatite is a calcium supplement, so the cautions are those of calcium: constipation, gas and bloating, and too much total calcium. Mild constipation affected 3.2% of 112 women over 4 years (Fernandez-Pareja 2007); the NIH says calcium carbonate causes more such effects than citrate, and smaller, more frequent doses or taking it with food can help (NIH ODS).

Lead is documented in calcium supplements, including bone-meal products. A survey of 70 brands found lead levels from 0.03 to 8.83 micrograms/g, with about 25% of products exceeding the FDA provisional tolerable intake for children aged 6 and under (Bourgoin 1993), and a later analysis found lead in natural and refined calcium carbonate products too (Ross 2000). Buy products with third-party contaminant testing.

Interactions are those of calcium. We found no interaction studies specific to hydroxyapatite.