Osteoporosis synergistically treated by bisphosphonates and Vitamin D - meta-analysis Nov 2024

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Efficacy of combination therapy of vitamin D and bisphosphonates in the treatment of postmenopausal osteoporosis: a systematic review and meta-analysis

Front Pharmacol 2024 Nov 21:15:1422062. doi: 10.3389/fphar.2024.142206
Yuangui Yang # 1, Mingyue Yang # 2, Xuanyi Su # 1, Feibin Xie 3

Objective: There is currently no consensus on whether the combination therapy of Vitamin D (VitD) and bisphosphonates offers superior efficacy compared to monotherapy in the treatment of postmenopausal osteoporosis. The aim of this study is to conduct a meta-analysis of recent relevant research to synthesize the available evidence and further investigate whether the combined use of VitD and bisphosphonates is superior to monotherapy in treating osteoporosis in postmenopausal women.

Methods and results: We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized controlled trials (RCTs) comparing the effects of monotherapy with VitD or bisphosphonates versus their combination therapy in the treatment of postmenopausal osteoporosis, up to 1 February 2024. The articles were independently screened and relevant data were extracted by two investigators. The changes in mean values and percentage changes for bone resorption markers, bone formation markers, bone mineral density, and bone mineral metabolism markers were expressed using the standardized mean difference (SMD) and 95% confidence intervals (CI). Heterogeneity was quantitatively described using the I2 test. Subsequently, sensitivity analyses were performed for data with significant heterogeneity. Subgroup analyses were conducted based on the type of monotherapy used, and potential publication bias was assessed.
The analysis revealed that the combination of VitD and bisphosphonates demonstrated a more pronounced effect in increasing alkaline phosphatase (ALP), 25-hydroxyvitamin D (25-OH-VD), and serum calcium (sCa) levels, as well as in decreasing levels of serum bone-specific alkaline phosphatase (sBALP), serum C-terminal telopeptide of type I collagen (sCTX), and urinary N-telopeptide of type I collagen (UriNTX) compared to the monotherapy group.
However, the combination of VitD and bisphosphonates did not show a significant advantage over monotherapy in terms of improving osteocalcin levels. The differences in the mean changes in osteocalcin, UriNTX, and sCa, as well as the percentage changes in parathyroid hormone (PTH) were not statistically significant (p > 0.05).

Conclusion: The meta-analysis suggests that compared to monotherapy, the combination therapy of VitD and bisphosphonates exhibits a more favorable effect on bone mineral density and bone calcium metabolism-related markers in the treatment of postmenopausal osteoporosis.
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VitaminDWiki – Overview Osteoporosis and vitamin D contains

• FACT: Bones need Calcium (this has been known for a very long time)
• FACT: Vitamin D improves Calcium bioavailability (3X ?)
• FACT: Should not take > 750 mg of Calcium if taking lots of vitamin D (Calcium becomes too bio-available)
• FACT: Adding vitamin D via Sun, UV, or supplements increased vitamin D in the blood
• FACT: Vitamin D supplements are very low cost
• FACT: Many trials, studies. reviews, and meta-analysis agree: adding vitamin D reduces osteoporosis
• FACT: Toxic level of vitamin D is about 4X higher than the amount needed to reduce osteoporosis
• FACT: Co-factors help build bones.
• FACT: Vitamin D Receptor can restrict Vitamin D from getting to many tissues, such as bones
• It appears that to TREAT Osteoporosis:
•        Calcium OR vitamin D is ok
•        Calcium + vitamin D is good
•        Calcium + vitamin D + other co-factors is great
•        Low-cost Vitamin D Receptor activators sometimes may be helpful
• CONCLUSION: To PREVENT many diseases, including Osteoporosis, as well as TREAT Osteoporosis
• Category Osteoporosis has 220 items
• Category Bone Health has 314 items

Note: Osteoporosis causes bones to become fragile and prone to fracture
  Osteoarthritis is a disease where damage occurs to the joints at the end of the bones

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VitaminDWiki – Osteoporosis category contains

• 220 items in category - see also Overview Osteoporosis and vitamin D
• Overview Fractures and vitamin D
• Bone - Health 314 items
• VitaminDWiki pages with BONE MINERAL DENSITY or BMD in title 29+ pages
• Search VitaminDWiki for OSTEOPENIA 1740 items as of July 2020
• 13 articles are in both Osteroporosis and Vitamin D Receptor categories
• 10 articles are in both Osteroporosis and Meta-analysis categories
• 20X increase in vitamin D sold and 36 percent decrease in osteoporosis business in Australia – Nov 2013

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How do bisphosphonates treat osteoporosis? asked Perplexity AI Dec 2024

Bisphosphonates are a class of drugs widely used to treat osteoporosis by slowing bone loss and reducing the risk of fractures. They work through several mechanisms to strengthen bones and prevent further deterioration:
Mechanism of Action
Bisphosphonates function primarily by inhibiting osteoclast-mediated bone resorption 3
These drugs have a high affinity for bone mineral, specifically hydroxyapatite crystals, allowing them to be selectively incorporated into sites of active bone remodeling 3
Osteoclast Inhibition

1. Apoptosis Induction: Bisphosphonates promote the apoptosis (programmed cell death) of osteoclasts, the cells responsible for breaking down bone tissue 3 5
2. Enzyme Inhibition: Nitrogen-containing bisphosphonates (such as alendronate, risedronate, ibandronate, and zoledronic acid) inhibit farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway 3 6

This inhibition disrupts the function and survival of osteoclasts.
Bone Remodeling Effects

1. Reduced Bone Turnover: By inhibiting osteoclast activity, bisphosphonates decrease the rate of bone resorption, allowing bone-forming osteoblasts more time to promote bone formation 3
2. Increased Bone Density: Treatment with bisphosphonates can lead to measurable increases in bone mineral density (BMD) over time 7

Efficacy in Osteoporosis Treatment
Bisphosphonates have demonstrated significant efficacy in treating osteoporosis:

1. Fracture Risk Reduction: They can reduce the risk of vertebral fractures by 60-70% within the first year of treatment 7
2. BMD Improvement: After 3 years of treatment, bisphosphonates can increase BMD by 5-7% in the spine and 1.6-5% in the femoral neck 7
3. Non-vertebral Fracture Prevention: Some bisphosphonates (alendronate, risedronate, and zoledronic acid) have shown a 20-30% reduction in non-vertebral fracture risk and a 40-50% reduction in hip fracture risk 7

Administration and Types
Bisphosphonates can be administered in various ways:

• Oral: Taken weekly (e.g., alendronate 70mg) or monthly (e.g., ibandronate 150mg) 1
• Intravenous: Administered yearly (e.g., zoledronic acid 5mg) 1 5

Long-term Effects
Bisphosphonates have a unique property of accumulating in the bone, allowing for persistent effects even after discontinuation. This has led to the concept of "drug holidays" for some patients after 3-5 years of treatment 2
.In conclusion, bisphosphonates treat osteoporosis by effectively reducing bone resorption, increasing bone density, and significantly lowering fracture risk, making them a cornerstone in the management of osteoporosis.

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56,900 studies contain Bisphosphonates AND osteoporosis AND "vitamin d" as of Dec 2024

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