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Which 2 drugs for osteoporosis tx have broad spectrum anti-fracture activity?

-Bisphosphonates (except Ibandronate=bonivia)

-Denosumab = prolia


-approved for
-side effects

-tx of osteoporosis only

intranasal -> 200 units or 1 spray/nostril daily
IM/subcut -> 100 units every other day

-Side effects
rhinitis, epistaxis (rare), nausea and flushing when given as injection

-2nd/3rd line

-has analgesic properties

-recommended for > 5 years post-men


-approved for
-side effects


2. Tx and prevention of osteoporosis

3. Oral, 60 mg daily

4. Hot flashes and inc risk for VTE

5. 2nd link

-doesn't increase risk of breast and uterine cancer unlike estrogen


-types and administration routes
-which one has highest affinity and potency?

1. Alendronate (Fosamax)
-can come with vitamin D 2600 or 5800 IU

2. Risedronate

3. Zoledronic acid -> highest potency and affinity

4. Ibandronate
-oral or IV


-side effects

-block farnesyl pyrophosphate synthase (FPPS) in osteoclasts

-poorly absorbed when taken PO
-excreted in urine unchanged

-esophageal irritation w/ oral
-acute phase tx w/ 1st injection
-acute renal failure with IV
-ONJ (rare)
-Atypical femur fractures (rare)

-Don't use in patients w/ creatinine clearance < 30 - 35 mL/min


-side effects

-inhibits RANKL which is needed for osteoclast differentiation

-subcut injections, 60mg every 6 months

-UTI/URI, skin rxns, hypercalcemia, MS pain, ONJ, AFF


Oral BPs vs Denosumab

-BPs should be 1st choice

-consider denosumab with:
older patients who have difficulty with the dosing requirements of oral bisphosphonates or in patients with renal insufficiency.


-dose route
-adverse effects including black box warning

-only anabolic agent for osteoporosis tx

-rPTH: increases bone turnover w/ net increase in bone being laid down

-daily injections

-use in patients who have failed to BPs

Adverse effects
1. Hypercalcemia – usually transient
2. OSTEOSARCOMA – black box warning
a. Can only use this drug 2 years in a lifetime
b. Contraindicated in patients with increased risk of OS
i. Paget’s disease
ii. Unexplained alk phos elevation
iii. Hx of radiation involving skeleton


Epidermolysis Bullosa
-site of blisters
-which one is worse?

1. Simplex (poor prognosis)
-K5 or 14 mutations
-In basal area
-rupture exposes dermis

2. Dystrophic
-K1 or 10 mutations
-blisters in s. spinosum


2 important characteristics of s. granulosum keratinocyte

o Lamellar bodies – specialized lipids for barrier/cement fx
o Keratin granules – protect/aggregate keratin filaments


Icthyosiform erythroderma

o Autosomal recessive
o No lamellar bodies
o Keratohyalin granules can be present in low numbers or absent
o Mild form – very thick stratum corneum
• Can be managed with retinoic acid which can regulate the differentiation of keratinocyte
• Reduce thickness of stratum corneum
o Severe form
• Usually lethal during birth
• Interlocking stratum corneum lead to stillborn


birbeck granules

• Dilated cisternae + trilaminar handles
• Trilaminar handle is continuous with plasma membrane of Langerhans cell
• Process of antigen presentation – IMPORTANT
• Brought in through clathrin-coated organelles -> chopped up and sent back out


-derived from?
-2 types of melanin?

o Derived from neural crest cells
o Transfer of melanosome to cells (keratinocytes) in skin ONLY
o 2 types of melanin
• Eumelanins
• Brown and black colors
• Pheomelanins
• Yellow and red
• Both are derived for tyrosine – IMPORTANT
• Tyrosinase shifts the tyrosine into the melanin producing pathway


Congenital albinism
-prognosis of each class

o Melanocytes can’t make pigment
o 2 major categories
• Tyrosinase negative
• Tyrosinase positive
• Check this using tyrosinase incubation test
• Tyrosinase negative individuals continue to be amelanotic
• Cancer prone, sensitive skin etc.
• Tyrosinase positive individuals do get improvement in skin as they age
• Better prognosis


2 etiologies for BM blistering diseases

• Autoimmune – attack molecular components and compromise integrity of BM
• Nucleotide lesions in genes that encoded BM protein
o Leads to fragile BM


Hernia terminology

1. Pantaloon - direct + indirect components

2. Richter's - contains antimesenteric portion of small bowel

3. Sliding - involves visceral peritoneum or an organ


Border's of Hesselbach's triangle

• Lateral edge of rectus muscle
o Linea semilunaris
• Inferior epigastric vessels
• Inguinal ligament (medial 1/2)


Femoral hernia occurs b/w

-high risk of?

o Medial to femoral vein and lateral to lacunar ligament



Hernia repair

• Suture transversalis fascia to inguinal ligament (Poupart’s)

• Similar to Bassini but more sutures

• Transversalis fascia to Cooper’s (pectineal) ligament

• Tension free repair – IMPORTANT
• Mesh is used to cover up the defect
• One edge sutured to inguinal ligament and the other to lateral edge of transversalis fascia
• Brings down recurrence rate of hernia significantly


Laparoscopic hernia repair done through

preperitoneal space

-for recurrent hernia
-for bilateral inguinal hernias (can do both at once)


Nerve at most increased risk of being damaged w/ hernia repair?

Ilioinguinal nerve


2 most common sites to do DEXA scan?

1. Spine (L1 - L4)
2. Hip


RDA for calcium

• 1 – 3 y/o -> 700 mg/day
• 1300 during puberty and a few years after that
• Women over 50 -> RDA has been increased
• 1200 for men > 70 and women > 50


RDA for vit D

• 1 – 3 y/o -> 600 IU/day
• This stays till age 70
• > 71 -> 800
• Pregnant/lactating -> 600
• There is an upper limit
• Infants
• AI -> 400
• UL -> 1000 – 1500


USPSTF recommendations for vit D and Ca supplementation

• Inadequate evidence to determine benefit of supplementation in premenopausal women or men
• Postmenopausal – inadequate evidence for > 400 IU of vit D and > 1000 mg of calcium
• Recommend against daily supplementation with less than 400 IU of vit and D and less than 1000 mg of Ca?


3 determinants of peak bone mass

• Height and weight – larger skeleton has more mineral

• Physical activity – very important for bones
• Weight bearing (impact loading)
• Strengthening (loads from bending and torsion)
• Affect fluid shifts

• Dietary intake


Bone scan agent accumulation in skeleton can depend on

-high osteogenic acitivity
-high blood flow
-interrupted sympathetic nerve supply


2 bone tumors more common in females than males?

-fibrous dysplasia

-giant cell tumor
-> location = knee EPIPHYSIS


-suggestive sign
-most common mets site

-distal femur/proximal tibia in medulla of bone

-Codman triangle

-Lucency on radiograph




-location: medulla of tubular bones of hands and feet most common



at the growth plate


-compare to osteosarcoma

-axial skeleton
-less common than OS and doesn't respond to chemo


Fibrous dysplasia
-number of tumors

1. Think of it as developmental arrest
2. Medulla of bones of adolescents and only one bone involved most commonly
3. If > 1 -> McCune Albright syndrome
4. More common in FEMALES than males
5. Histology
a. Mostly woven bone in varying densities
b. Chinese character type of bone formation


Ewing sarcoma
-histology (including Ab staining)

-location: medulla of diaphysis of long bones and pelvic flat bones

-imaging: destructive lytic tumor w/ onion-skin periosteal rxn

a. Looks like lymphoma
b. Cells w/ round dark nuclei and little cytoplasm
c. CD99 antibody – stains cell membranes of cancerous cells
d. Cytogenic analysis can also be done to check for translocation
i. Breakapart FISH



1. Most common soft tissue sarcoma in kids
2. Location – head and neck
3. Malignant soft tissue tumor
4. Histology
a. Loosely resemble muscle cells
b. “strap cells”

-p53 mutation (Li-Fraumeni syndrome)


Steps of the fracture callous


-inflammatory cells

-osteoclast activity goes up

-granulation tissue laid down

-soft callus -> woven bone

-hard callus -> calcification

-remodeling -> lamellar bone


Legg-Calve-Perthes Disease
-what happens?

i. Affects children
ii. Loss of blood supply to femoral head -> ischemic necrosis


Chalkstick fracture associated with?

i. Associated with Paget’s disease
1. Excessive breakdown and formation of bone leading to bone weakness
ii. Completely transverse fractures (clean break)
iii. Also applied to transverse spinal fractures in alkylosing spondylitis


Dx of S. aureus based on

o Fever, HypoTN, rash + 3 of major organ symptoms


-most common hematogenous cause
-other causes

• IMPORTANT – staphylococcus aureus is the most common cause of overall hematogenous osteomyelitis
• If patient is sexually active -> consider N. gonorrhoeae
• Diabetic and druggies -> Pseudomonas aeruginosa
• SCD -> Salmonella
• Prosthetic joint replacement -> S. aureus and S. epidermidis
• Tb -> M. tuberculosis
• Hits the vertebrae


Infectious (septic) arthritis
-spread through
-most common cause

• Spread through hematogenous route
• N. gonorrhoeae and S. aureus most common cause in adults


Streptococcal TSS associated with?
-bacteremic (y/n)
-serious complication?

production of streptococcal pyrogenic toxins

-most are bacteremic

-necrotizing fasciitis


Receptors for exfoliating toxins only seen in?

what do they do?


-scalded skin syndrome
• Toxin reaches stratum granulosum and disrupts intracellular bridges b/w these cells and the epidermis
• Epidermis sloughs off


Metastatic foci for staph aureus

• Bone (osteomyelitis)
• Joints (septic arthritis)


Boundaries of inguinal canal
-roof/floor (superior/inferior)

• Deep -> deep inguinal ring

• Superficial -> superficial inguinal ring

• Anterior -> aponeurosis of the external abdominal oblique muscle

• Inferior (floor) -> inguinal ligament and lacunar ligament

• Superior (roof) -> the arching fibers of the internal abdominal oblique and transverse abdominis muscle
• Conjoint tendon

• Posterior -> transversalis fascia (contains DIR)
• Reinforced medially by the conjoint tendon


-Intercostal nerves
-subcostal nerves
-iliohypogastric nerve
-ilioinguinal nerve

1. T7 - T11

2. T12

3. T12 and L1

4. L1


Important dermatomes for anterolateral abdominal wall

• T7 -> skin overlying tip of xyphoid process
• T10 -> skin of the umbilicus
• T12 -> skin superior pubic symphysis
• L1 -> skin overlying pubic symphysis


superficial epigastric vein anastomoses with?

serves as collateral venous channel from what to what?

-lateral thoracic vein in superficial fascia

-femoral vein to axillary vein