osteoporosis – controversies and promising treatment options

Keith R. Holden, M.D.

Ponte Vedra Beach, FLwww.Dr-Holden.com

Guidelines for prevention and tx vary

Bone quality versus bone quantity

Same BMD can have different fx risk (age)

Cumbersome dosing requirements

Drug side effects

Esophagitis

Esophageal stricture

Esophageal cancer

Osteonecrosis of jaw

Atypical Femur Fracture

Bisphosphonates ↓ osteoclast fxn & induce osteoclast apoptosis

Suppress bone resorption = hard, brittle bone

Path: ↓ bone heterogeneity = ↓ bone quality Complete lack of TCN labeling = severe ↓ bone formation Stress injury-like cortical hypertrophy in other femur with

unilateral AFF

↑ BMD does not always = ↑ bone strength

T-score not consistent predictor of osteoporosis outside of elderly postmenopausal white♀

Other populations, Z score may be better predictor of low bone density

www.shef.ac.uk/FRAX/tool.jsp

FRAX estimates 10-yr. fx risk based on BMD femoral neck + osteo risk factors

Bone quality = bone strength (cortical bone structure/quality of collagen) + rate of remodeling

Bone densitometry measures BMD (quantity), helps assess fx risk, aids in dx of osteo, but does NOT measure bone quality

Healthy bone requires a balance of:

Bone building by osteoblasts

Resorption by osteoclasts

90% collagen (majority Type 1)

Osteoclast degradation & osteoblast synthesis create circulating peptides of Type 1 collagen

Type I collagen is cross-linked by deoxypyridinoline (DPD)

DPD provides rigidity and strength (quality) to bone

Reflects bone remodeling yrs. before BMD ∆

↑ T score + ↑ biomarker → fx risk (odds 4.1)

Allow tracking of response to therapy

May improve adherence to therapy

Cross-link Type IC (relatively selective)

Measure of bone resorption - ↑ urine level > bone loss

Unaffected by diet

Easy to measure spot AM urine

Recheck within 30-90 days after initiating therapy

Covered by Medicare

Calcium Vitamin D Magnesium Boron Strontium ranelate Ipriflavone Vitamin K Choline stabilized orthosilicic acid (ch-OSA)

Ch-OSA = bioavailable silicon

RDBPC trial: added to calcium and D3 showing improved bone biomarkers and BMD ↑ 2%

RDBPC trial: ↑ tensile strength of hair

RDBPC trial: + effects of skin surface changes, mechanical properties, ↓ brittleness hair/nails

Pulsed Electromagnetic Field (PEMF) therapy has shown promise in clinical trials for tx and prevention of osteoporosis

Mediates process via cell signaling proteins – growth factors, cytokines, and prostaglandins

PEMF 72Hz 10 hrs daily for 12 wks to radius of “osteoporosis prone” ♀

BMD showed sig. inc. in exposed areas 36 wks

Similar but weaker response in non-treated arm

(Tabrah, et. al., 1990)

Evaluated rats with surgically induced DOP

After 8 wks, PEMF sig. ↑BMD, ↑ TGF-beta 1, ↓IL-6 in proximal femur

Conclusion: PEMF efficiently suppresses bone loss in DOP via local factors

(Shen, et al., 2010)

Evaluated CR with PEMF in ovariectomy-induced osteoporosis in rats

12 weeks, (OVX-DPEMF) group had better prevention against OVX-induced bone loss

↑BMD, ↑osteoblast activity, ↑ trabecular health markers; ↓bone markers of resorption (uDPD)

(Jing, et. al., 2010)

Rats with streptozotocin-induced DM bone loss

PEMF daily 8 hrs x 8 wks

PEMF improved biomechanical bone quality DM bone

PEMF partially reversed DM-induced bone deterioration

Conclusion: PEMF might become an additive method for inhibiting DM osteoporosis

(Jing, et al., 2011)

Study on in-vitro osteoblastic cell culture

PEMF ↑osteoblastic growth, ↑ TGF-beta 1

PEMF ↓ prostaglandin E2

Conclusion: Study sheds light on mechanism of action of PEMF in non-union fx & prevention of osteoporosis

(Li, et al., 2007)

Studied rats subjected to bil ovariectomy

PEMF augmented/restored trabecular bone mass/architecture in PEMF groups

PEMF attenuated higher serum PGE(2) of OVX rats and restored levels to that of controls

Conclusion: PEMF may be useful in prevention of osteoporosis resulting from ovariectomy

(Chang, et al., 2003)

PTH used to tx osteoporosis; Insulin & IGF-1 anabolic roles in osteogenesis

Cell signaling proteins IRS-1, S6 RSK, & eNOS were phosphorylated by PTH, Insulin, & PEMF to the same extent in osteoblast-like cells

Conclusion: Anabolic affects of PEMF may be mediated through these proteins

(Schnoke, et. al., 2007)

↑ BMD

↑ TGF-beta 1

↓ IL-6

↓ PGE(2)

↑ osteoblast growth

Phosphorylation of IRS-1, S6 RSK, eNOS

Alkalinizing plant based diet

Address food sensitivities Mineral rich foods

Remove

Replace

Reinnoculate

Repair

Rebalance

Foci of interference (ANS) Stress Inflammation Toxins Allergy Infection (occult, dysbiosis, dental) Heavy metals

Resistance training

Nutritional supplementation

Hormonal balance

PEMF

66 y.o ♀ with osteoporosis (T-score -3.1) Baseline: mostly plant based diet,

resistance training, Ca, Mg, and D (1/27/11) uDPD 9.7 nM/mM Cr (NL < 6.5) Weekly 1 hr PEMF sessions x 2 mos

(3/16/11) uDPD 4.5 (53% drop!) Maintenance: Monthly 1 hr PEMF

(7/21/11) uDPD 5.5 (10/24/11) uDPD 4.5

63 y.o. ♀ osteoporosis (‘09 T-score LS -3.9; ‘11 T-score LS -4.1)

Hx FMG, CFS, IBS, MCS & hx multiple fxs Baseline: BHRT, Ca, Mg, D Added ch-OSA + tx gut dysbiosis Started PEMF (3/26/11) monthly; (7/26/11) inc.

freq. to weekly; (9/12/11) 2-3 X week (4/13/11) uDPD 9.7; (10/4/11) uDPD 5.0

(48.45% drop!)

Keith R. Holden, M.D.

822 A1A North, Suite 310Ponte Vedra Beach, FL 32082

(904) 473-4954krholden@gmail.com

www.Dr-Holden.com