Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through D-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study
D
Non-RDBPC human or In-vivo animal trials
 

Introduction

This protocol provides evidence-based guidance to support bone health and reduce fracture risk in adults by translating the Council for Responsible Nutrition (CRN) Supplements to Savings report into practical, accessible nutritional interventions for providers.

Ingredients

Calcium Citrate

Dosing: 1,000–1,200 mg total per day (from diet and supplements combined) (White 2022)

  • Note: Osteoporosis primarily affects older adults, a population in which hypochlorhydria (low stomach acid) is common. While calcium carbonate is commonly used in research and supplements, it requires adequate stomach acid for absorption. For this reason, calcium citrate is preferred in osteoporosis protocols because it is well absorbed regardless of stomach acid and generally better tolerated. To further maximize absorption, calcium supplementation should not exceed 500–600 mg per dose. (Camacho 2020)

Supporting evidence:

  • A meta-analysis of 29 randomized controlled trials (RCTs) (n=63,897; mean age >50) found that calcium (>1,200 mg per day) or calcium plus vitamin D (>800 IU per day) supplementation reduced the risk of all fractures by 12%. In trials that reported bone-mineral density (BMD) as an outcome, supplementation was associated with a reduced rate of bone loss at the hip (0.54%) and in the spine (1.19%). Higher compliance and dosage were associated with greater benefit. (Tang 2007)
  • This meta-analysis of 32 controlled trials involving 3,169 postmenopausal women found that calcium supplementation (around 1,000 mg per day) helped significantly slow bone loss compared to controls. Women not receiving supplements lost an average of 1.07% of bone mass per year, while those on calcium lost only 0.27% annually. Importantly, the benefit of supplementation did not vary by anatomical site; similar effects were observed at the spine, proximal femur, forearm/hand, and total body. The protective effect of calcium against bone loss through ongoing supplementation was evident for up to four years, after which its impact diminished. (Nordin 2009)
  • The National Osteoporosis Foundation performed a more recent meta-analysis of eight RCTs with 30,970 community-dwelling and institutionalized middle-aged to older adults. The authors supported using supplemental calcium and vitamin D (500–1,200 mg per day and 400–800 IU per day, respectively) based on evidence that showed they reduced total fracture risk by 15% and hip fracture risk by 30%. (Weaver 2016)
  • In a two-year randomized, double-blind trial of 323 healthy men over age 40 (mean age 57), daily supplementation with 1,200 mg of calcium (but not 600 mg) led to modest increases in BMD (1–1.5% greater than placebo). This higher dose was also associated with sustained reductions in serum parathyroid hormone (–25%), total alkaline phosphatase (ALP) activity (–8%), and procollagen type I N-terminal propetide (PINP) (–20%). Falls tended to occur less frequently in the 1,200 mg group than in the 600 mg and placebo groups. (Reid 2008)
  • A double-blind, placebo-controlled trial in 159 postmenopausal women found that daily calcium supplementation significantly reduced serum markers of bone turnover (cross-linked C-telopeptide (CTX) and PINP) over six months. These reductions were not observed with vitamin D supplementation alone, indicating a direct effect of calcium on bone turnover dynamics. (Aloia 2013)
Calcium Citrate in the Fullscript catalog

Vitamin D

Dosing: At least 600 IU daily, ongoing (White 2022)

Supporting evidence:

  • A meta-analysis of randomized controlled trials found that vitamin D3 supplementation yielded modest yet statistically significant increases in BMD at the lumbar spine (standard mean difference (SMD) = 0.06) and femoral neck (SMD = 0.25), with a linear dose-response relationship also extending to the total hip. The effect was more pronounced in older adults, postmenopausal women, and individuals with lower baseline serum vitamin D levels. (Kazemian 2023)
  • A meta-analysis pooling data from 42 RCTs involving adults aged 19–84 years found that vitamin D supplementation significantly reduced the bone resorption marker deoxypyridinoline (DPD) (weighted mean difference (WMD) –1.58 nmol/mmol). Subgroup analyses showed that PINP decreased in individuals over 50 years, and ALP was substantially reduced when supplementation lasted longer than 12 weeks. (Sohouli 2023)
  • An umbrella review evaluated 13 meta-analyses on vitamin D supplementation and its effects on falls and fractures. The findings indicate that combined vitamin D and calcium supplementation may help reduce fall risk compared with calcium alone or placebo. The strongest evidence supports a 16–33% reduction in hip fracture risk and a 5–19% reduction in any fracture risk, particularly among institutionalized individuals. (Chakhtoura 2020)
Vitamin D in the Fullscript catalog

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

View protocol on Fullscript
References
  1. Aloia, J. F., Dhaliwal, R., Shieh, A., et al. (2013). Calcium and Vitamin D Supplementation in Postmenopausal Women. The Journal of Clinical Endocrinology & Metabolism, 98(11), E1702–E1709. https://doi.org/10.1210/jc.2013-2121
  2. Camacho, P. M., Petak, S. M., Binkley, N., et al. (2020). AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS—2020 UPDATE. Endocrine Practice, 26(Supplement 1), 1–46. https://doi.org/10.4158/gl-2020-0524suppl
  3. Cauley, J. A. (2013). Public Health Impact of Osteoporosis. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 68(10), 1243–1251. https://doi.org/10.1093/gerona/glt093
  4. Chakhtoura, M., Chamoun, N., Rahme, M., et al. (2020). Impact of vitamin D supplementation on falls and fractures—A critical appraisal of the quality of the evidence and an overview of the available guidelines. Bone, 131, 115112. https://doi.org/10.1016/j.bone.2019.115112
  5. Clynes, M. A., Harvey, N. C., Curtis, E. M., et al. (2020). The Epidemiology of Osteoporosis. British Medical Bulletin, 133(1), 105–117. https://doi.org/10.1093/bmb/ldaa005
  6. Gill, T. M., Murphy, T. E., Gahbauer, E. A., et al. (2013). Association of injurious falls with disability outcomes and nursing home admissions in community-living older persons. American Journal of Epidemiology, 178(3), 418–425. https://doi.org/10.1093/aje/kws554
  7. Kazemian, E., Pourali, A., Sedaghat, F., et al. (2023). Effect of supplemental vitamin D3 on bone mineral density: a systematic review and meta-analysis. Nutrition Reviews, 81(5), 511–530. https://doi.org/10.1093/nutrit/nuac068
  8. Morin, S. N., Leslie, W. D., & Schousboe, J. T. (2025). Osteoporosis: A Review. JAMA. https://doi.org/10.1001/jama.2025.6003
  9. Nordin, B. E. C. (2009). The effect of calcium supplementation on bone loss in 32 controlled trials in postmenopausal women. Osteoporosis International, 20(12), 2135–2143. https://doi.org/10.1007/s00198-009-0926-x
  10. Reid, I. R., Ames, R., Mason, B., et al. (2008). Randomized Controlled Trial of Calcium Supplementation in Healthy, Nonosteoporotic, Older Men. Archives of Internal Medicine, 168(20), 2276–2282. https://doi.org/10.1001/archinte.168.20.2276
  11. Sohouli, M. H., Wang, S., Almuqayyid, F., et al. (2023). Impact of vitamin D supplementation on markers of bone turnover: Systematic review and meta‐analysis of randomised controlled trials. European Journal of Clinical Investigation, 53(10), e14038. https://doi.org/10.1111/eci.14038
  12. Tang, B. M., Eslick, G. D., Nowson, C., et al. (2007). Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. The Lancet, 370(9588), 657–666. https://doi.org/10.1016/s0140-6736(07)61342-7
  13. Weaver, C. M., Alexander, D. D., Boushey, C. J., et al. (2015). Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporosis International, 27(1), 367–376. https://doi.org/10.1007/s00198-015-3386-5
  14. White, L. (2022). Osteoporosis Prevention, Screening, and Diagnosis: ACOG Recommendations. American Family Physician, 106(5), 587–588. https://www.aafp.org/pubs/afp/issues/2022/1100/practice-guidelines-osteoporosis.html